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Lu Z, Yan J, Zeng J, Zhang R, Xu M, Liu J, Sun L, Zu G, Chen X, Zhang Y, Pei R, Cao Y. Time-resolved T 1 and T 2 contrast for enhanced accuracy in MRI tumor detection. Biomaterials 2025; 321:123313. [PMID: 40187097 DOI: 10.1016/j.biomaterials.2025.123313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/30/2025] [Accepted: 03/31/2025] [Indexed: 04/07/2025]
Abstract
Stimuli-responsive contrast agents (CAs) have shown great promise in enhancing magnetic resonance imaging (MRI) for more accurate tumor diagnosis. However, current CAs still face challenges in achieving high accuracy due to their low specificity and contrast signals being confounded by potential endogenous MRI artifacts. Herein, an extremely small iron oxide nanoparticle (ESIONP)-based smart responsive MRI contrast agent (LESPH) is proposed, which is meticulously designed with sequential dual biochemical stimuli-initiated, time-resolved T1 and T2 contrast presentation, ensuring high tumor specificity while minimizing interference from endogenous artifacts. LESPH is constructed using emulsion solvent evaporation by assembling poly(2-(hexamethyleneimino) ethyl methacrylate) terminally conjugated with a disulfide bond-linked catechol group (DSPH)-modified ESIONPs, with lauryl betaine serving as a surfactant. When LESPH undergoes sequential responses to the weak acidity and high-concentration glutathione (GSH) in the tumor microenvironment, it experiences an extremely rapid transition from sparse ESIONP assemblies to dispersed ESIONPs, followed by a slower transition to closely aggregated ones, concomitantly providing distinguishable brightening and darkening contrast enhancement at the tumor location on different time scales. By virtue of its sequential dual responsiveness and time-resolved distinguishable contrast enhancements, LESPH successfully detects tumors with extremely high accuracy, providing a novel paradigm for the precise medical diagnosis of cancer.
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Affiliation(s)
- Zhongzhong Lu
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230000, China; CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Jincong Yan
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230000, China; CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Jianxian Zeng
- Department of Radiology, First Affiliated Hospital of Soochow University, Suzhou, 215026, China
| | - Ruihao Zhang
- Department of Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215026, China
| | - Mingsheng Xu
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Jihuan Liu
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Lina Sun
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Guangyue Zu
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Xiaomin Chen
- Department of Stomatology, Traditional Chinese Medicine Hospital of Kunshan, Kunshan, 215300, China
| | - Ye Zhang
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
| | - Renjun Pei
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230000, China; CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
| | - Yi Cao
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230000, China; CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
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Reja S. A simple, scalable protocol for the synthesis of ricinoleic acid-functionalised superparamagnetic nanoparticles with tunable size, shape, and hydrophobic or hydrophilic properties. NANOSCALE ADVANCES 2025:d5na00150a. [PMID: 40417165 PMCID: PMC12096511 DOI: 10.1039/d5na00150a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Accepted: 05/05/2025] [Indexed: 05/27/2025]
Abstract
Vegetable oils such as oleic acid have been widely used in the synthesis of nanomaterials as they are environmentally benign, cheap, and biodegradable. Ricinoleic acid (RA), which differs from oleic acid by the presence of an additional hydroxyl group, has surprisingly remained unexplored in the preparation of metal oxide nanoparticles, although it offers the advantage over oleic acid of easy functionalization due to the presence of the hydroxyl group. Here is a simple one-pot procedure for the synthesis of a variety of superparamagnetic nanoparticles, iron oxides and ferrites, using RA both as a precursor complexing agent and as a capping agent outlined. This procedure overcomes the challenges associated with the traditional thermal decomposition method, which demands separate precursor preparation and purification steps, thus promoting a simple yet scalable economic production of various magnetic nanoparticles. Minor changes in the reaction conditions allowed for the production of nanoparticles with different sizes, ranging from 5 to 17 nm, as well as different shapes, spherical and cuboid. Iron oxide nanospheres with an average particle size of 10 nm were superparamagnetic at room temperature with a saturation magnetization of 41 emu g-1. The as-prepared RA-coated nanoparticles are hydrophobic and dispersible in non-polar solvents but may easily be rendered hydrophilic and water dispersible; epoxidation, followed by alkaline ring-opening, produced hydroxylated nanoparticles with a positive zeta potential of 31 eV, whereas exchange of the capping RA with nitrilotriacetic acid (NTA) gave nanoparticles with a negative zeta potential of -25 eV. The present study highlights the uniqueness of using RA in the preparation of magnetic nanoparticles; apart from the ease and economics of scaling, it offers the possibility of the nanoparticles being either hydrophobic or hydrophilic.
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Affiliation(s)
- Sohel Reja
- Department of Inorganic and Physical Chemistry, Indian Institute of Science Bangalore Karnataka 560012 India
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3
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AlMatri E, Madkhali N, Mustafa S, Lemine OM, Algessair S, Mustafa A, Ali R, El-Boubbou K. Preparation, Characterization, and Antibacterial Activity of Various Polymerylated Divalent Metal-Doped MF 2O 4 (M = Ni, Co, Zn) Ferrites. Polymers (Basel) 2025; 17:1171. [PMID: 40362955 PMCID: PMC12073262 DOI: 10.3390/polym17091171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 04/19/2025] [Accepted: 04/22/2025] [Indexed: 05/15/2025] Open
Abstract
The continuous discovery of novel effective antibacterial agents using nano-based materials is of high significance. In this study, we utilized Polymerylated divalent-metal-doped ferrite nanoparticles (PMFe2O4 NPs) and studied their antibacterial inhibition effects. Different panels of PVP- and PEG-coated metal-doped MFe2O4 (M ≅ Co, Ni, and Zn) were prepared via the Ko-precipitation Hydrolytic Basic (KHB) methodology and thoroughly analyzed using TEM, XRD, FTIR, and VSM. The as-synthesized doped ferrites displayed stable quasi-spherical particles (7-15 nm in size), well-ordered crystalline cubic spinel phases, and high-saturation magnetizations reaching up to 68 emu/g. The antibacterial efficacy of the doped ferrites was then assessed against a Gram-negative E. coli bacterial strain. The results demonstrated that both metal doping and polymer functionalization influence the antimicrobial efficacies and performance of the ferrite NPs. The presence of the PVP polymer along with the divalent metal ions, particularly Co and Ni, resulted in the highest antibacterial inhibition and effective inactivation of the bacterial cells. The antibacterial performance was as follows: PVP-CoFe2O4 > PVP-NiFe2O4 > PVP-ZnFe2O4. Lastly, cell viability assays conducted on human breast fibroblast (HBF) cells confirmed the good safety profiles of the doped ferrites. These interesting results demonstrate the distinctive inhibitory features of the biocompatible metal-doped ferrites in enhancing bacterial killing and highlights their promising potential as effective antimicrobial agents, with possible applications in areas such as water disinfection, biomedical devices, and antimicrobial coatings.
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Affiliation(s)
- Enas AlMatri
- Department of Chemistry, College of Science, University of Bahrain, Bahrain 32038, Bahrain;
| | - Nawal Madkhali
- Department of Physics, College of Science, Imam Mohammad Ibn Saud Islamic University (IMISU), Riyadh 11623, Saudi Arabia; (N.M.); (O.M.L.); (S.A.)
| | - Sakina Mustafa
- Department of Biology, College of Science, University of Bahrain, Bahrain 32038, Bahrain;
| | - O. M. Lemine
- Department of Physics, College of Science, Imam Mohammad Ibn Saud Islamic University (IMISU), Riyadh 11623, Saudi Arabia; (N.M.); (O.M.L.); (S.A.)
| | - Saja Algessair
- Department of Physics, College of Science, Imam Mohammad Ibn Saud Islamic University (IMISU), Riyadh 11623, Saudi Arabia; (N.M.); (O.M.L.); (S.A.)
| | - Alia Mustafa
- Department of Physics, College of Science, University of Bahrain, Bahrain 32038, Bahrain;
| | - Rizwan Ali
- Medical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh 11481, Saudi Arabia;
| | - Kheireddine El-Boubbou
- Department of Chemistry, College of Science, University of Bahrain, Bahrain 32038, Bahrain;
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4
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Yu J, Li S, Zhu X, Yu H, Gao H, Qi J, Ying Y, Qiao L, Zheng J, Li J, Che S. Ultra-Small Iron-Based Nanoparticles with Mild Photothermal-Enhanced Cascade Enzyme-Mimic Reactions for Tumor Therapy. MATERIALS (BASEL, SWITZERLAND) 2025; 18:1649. [PMID: 40271909 PMCID: PMC11990581 DOI: 10.3390/ma18071649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 03/30/2025] [Accepted: 03/31/2025] [Indexed: 04/25/2025]
Abstract
Chemodynamic therapy (CDT), which utilizes the catalytic reactions of nanoparticles to inhibit tumor growth, is a promising approach in cancer therapy. However, its efficacy is limited by insufficient hydrogen peroxide (H2O2) concentration in tumor microenvironments and unsatisfactory enzymatic catalytic activity. To overcome these limitations, ultra-small iron-based (USIB) nanoparticles with cascaded superoxide dismutase (SOD)-mimic and peroxidase (POD)-mimic activities have been engineered. USIB nanoparticles initiated by SOD-mimic activity to transform superoxide anions (O2·-) into H2O2, elevating H2O2 levels in the tumor microenvironment and subsequently utilizing POD-mimic activity to convert H2O2 into the more reactive ·OH, thereby achieving the destruction of tumor cells. In addition, USIB nanoparticles possess photothermal conversion capabilities, and their enzymatic activity can be significantly enhanced under mild laser irradiation. Therefore, by addressing the issues of insufficient substrate concentration and low enzymatic catalytic activity, the therapeutic efficiency of CDT has been improved. Our research integrates the cascade catalytic reactions of nanozymes with laser irradiation, effectively inhibiting tumor growth and exhibiting outstanding biosafety, demonstrating promising therapeutic potential.
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Affiliation(s)
- Jing Yu
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Shuangshan Li
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Xun Zhu
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Hongyan Yu
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Hao Gao
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Jiarui Qi
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Yao Ying
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Liang Qiao
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Jingwu Zheng
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Juan Li
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Shenglei Che
- Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou 310014, China; (S.L.); (X.Z.); (H.Y.); (H.G.); (J.Q.); (Y.Y.); (L.Q.); (J.Z.); (J.L.)
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
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5
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Song X, Xu L, Li L, Meng X, Wang Y, Qiu L, Hu Y, Zhang M, Xiang L, Xi G, Wu A, Wang X, Lin J. Amorphous/Crystalline Urchin-Like TiO 2 SERS Platform for Selective Recognition and Efficient Identification of Glutathione. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2409400. [PMID: 39797480 DOI: 10.1002/smll.202409400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/30/2024] [Indexed: 01/13/2025]
Abstract
Glutathione serves as a common biomarkers in tumor diagnosis and treatment. The levels of its intracellular concentration permit detailed investigation of the tumor microenvironment. However, low polarization and weak Raman scattering cross-section make direct and indirect Raman detection challenging. This study designs an amorphous-crystalline urchin-like TiO2 (AC-UL-TiO2) for the accurate identification of GSH and GSSG. By synergistically regulating the crystalline core and amorphous shell, the bandgap structure is optimized, thereby enhancing charge transfer efficiency. AC-UL-TiO2 demonstrates excellent SERS performance in detecting dye molecules with good selectivity for mixed analytes. The enhancement factor (EF) for R6G is 6.89 × 106, and the limit of detection (LOD) is 10-10 M. A SERS-colorimetric dual-modality platform is developed based on the AC-UL-TiO2@DTNB system to accurately monitor GSH concentrations from 0 to 1000 µM, providing a robust dual-confirmation result. Importantly, combined with the principal component analysis method, the AC-UL-TiO2 SERS platform can directly distinguish GSH and GSSG molecules. Besides, direct SERS detection LOD for GSH and GSSG are 10-8 M, which is 100 times higher than that of indirect detection. These findings indicate that AC-UL-TiO2 holds potential for biomarkers trace detection in tumor microenvironments.
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Affiliation(s)
- Xiaoyu Song
- School of Chemistry, Beihang University, Beijing, 100191, China
- Key Laboratory of Consumer Product Quality Safety Inspection and Risk Assessment for State Market Regulation, Chinese Academy of Inspection and Quarantine, Beijing, 100176, China
| | - Lei Xu
- Ningbo Institute of Materials Technology and Engineering, CAS, Chinese Academy of Science, Ningbo, 315201, China
| | - Longsong Li
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Xiangyu Meng
- School of Chemistry, Beihang University, Beijing, 100191, China
| | - Yuening Wang
- School of Chemistry, Beihang University, Beijing, 100191, China
| | - Lin Qiu
- School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Yue Hu
- Ningbo Institute of Materials Technology and Engineering, CAS, Chinese Academy of Science, Ningbo, 315201, China
| | - Mingjian Zhang
- School of Chemistry, Beihang University, Beijing, 100191, China
| | - Lingchao Xiang
- Ningbo Institute of Materials Technology and Engineering, CAS, Chinese Academy of Science, Ningbo, 315201, China
| | - Guangcheng Xi
- Key Laboratory of Consumer Product Quality Safety Inspection and Risk Assessment for State Market Regulation, Chinese Academy of Inspection and Quarantine, Beijing, 100176, China
| | - Aiguo Wu
- Ningbo Institute of Materials Technology and Engineering, CAS, Chinese Academy of Science, Ningbo, 315201, China
| | - Xiaotian Wang
- School of Chemistry, Beihang University, Beijing, 100191, China
| | - Jie Lin
- Ningbo Institute of Materials Technology and Engineering, CAS, Chinese Academy of Science, Ningbo, 315201, China
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6
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Lu C, Bao Y, Fei Z, Wang Z, Ma J, Ren R, Xu X, Zhang Y. Multielement Doping Engineered Iron Oxide Nanoparticles: Enabling the Shift from Negative to Positive MRI Contrast for Enhanced Diagnostic Precision. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2410414. [PMID: 39981967 DOI: 10.1002/smll.202410414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/23/2025] [Indexed: 02/22/2025]
Abstract
Contrast-enhanced magnetic resonance imaging (CE-MRI) is a crucial tool for the diagnosis and management of various diseases globally. Iron oxide nanoparticles with sizes less than 5 nm are expected to address the long-term toxicity and brain accumulation issues associated with clinical gadolinium-based T1 contrast agents (GBCAs) due to their non-toxicity and biodegradability. However, synthesizing sub-5-nanometer particles presents significant challenges that complicate their clinical translation. Herein, traditional iron oxide-based negative (T2) agents into positive (T1) agents are transformed and an all-in-one multielement doping strategy is developed. Multiple elements into iron oxide crystals are introduced to form multielement doping engineered iron oxide nanoparticles (MDE-IONPs) and their surfaces with flexible hydrophilic ligands are subsequently modified. It is shown that Ni (II) and Gd (III) doping engineered nanoparticles can effectively enhance imaging efficacy, reducing clearance rates, and enabling controlled synthesis. Ultimately, the implementation of Ni (II) and Gd (III) co-engineering yield longitudinal relaxivity of up to 14.7 mM-1s-1 even for particles as large as 9 nm, an improvement of approximately 300% over GBCAs. Combined with the stability, biosafety, both in vitro and in vivo results suggest that all-in-one multielement doping is a favorable strategy for advancing the development of next-generation safe MRI contrast agents.
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Affiliation(s)
- Chichong Lu
- Department of Chemistry, College of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, China
| | - Yingjie Bao
- Department of Chemistry, College of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, China
| | - Zihan Fei
- Department of Chemistry, College of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, China
| | - Zhijie Wang
- CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Junjie Ma
- Department of Chemistry, College of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, China
| | - Ruimin Ren
- Department of Chemistry, College of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, China
| | - Xue Xu
- Department of Chemistry, College of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, China
| | - Yang Zhang
- Department of Chemistry, College of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, China
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7
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Moiseeva EO, Skribitsky VA, Finogenova YA, German SV, Shpakova KE, Sergeev IS, Terentyeva DA, Sindeeva OA, Kulikov OA, Lipengolts AA, Grigorieva EY, Gorin DA. Ultrasmall maghemite nanoparticles as MRI contrast agent: Unique combination of aggregation stability, low toxicity, and tumor visualization. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2025; 65:102811. [PMID: 40024489 DOI: 10.1016/j.nano.2025.102811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 01/30/2025] [Accepted: 02/11/2025] [Indexed: 03/04/2025]
Abstract
Iron oxide nanoparticles are a promising candidate for the dual-mode MRI contrast agent, however most of them have limited circulation time and predominant negative contrast. We developed citric acid stabilized superparamagnetic maghemite nanoparticles (CA-SPMNs) with size 3.2 ± 0.7 nm with intense positive contrast. Co-precipitation reactions under well-controlled conditions in the automatic chemical reactor have carried out the synthesis. We found an encouraging correlation between aggregate formation kinetics in biological media and in vitro cytotoxicity results and in vivo circulation time. A cytotoxicity test showed the mouse fibroblast viability over 80 % for iron doses exceeding 1 mg/mL. CA-SPMNs have a low r2/r1 ratio, exhibiting positive contrast. Using in vivo MRI we demonstrated that CA-SPMNs circulate in the blood for 12-24 h, enabling blood vessel and tumor visualization, and partial renal clearance. Finally, CA-SPMNs show promise as effective MRI contrast agents, enabling differentiation between normal and pathological tissues.
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Affiliation(s)
- Ekaterina O Moiseeva
- Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia
| | | | - Yulia A Finogenova
- N.N. Blokhin National Medical Research Center of Oncology, 115522 Моscow, Russia
| | - Sergei V German
- Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia.
| | - Kristina E Shpakova
- N.N. Blokhin National Medical Research Center of Oncology, 115522 Моscow, Russia
| | - Igor S Sergeev
- Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia
| | - Daria A Terentyeva
- Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia
| | - Olga A Sindeeva
- Vladimir Zelman Center for Neurobiology and Brain Rehabilitation, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia
| | - Oleg A Kulikov
- Institute of Medicine, National Research Ogarev Mordovia State University, 430005 Saransk, Russia
| | - Alexey A Lipengolts
- N.N. Blokhin National Medical Research Center of Oncology, 115522 Моscow, Russia
| | - Elena Yu Grigorieva
- N.N. Blokhin National Medical Research Center of Oncology, 115522 Моscow, Russia
| | - Dmitry A Gorin
- Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia
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8
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Parambath JBM, Vijai Anand K, Ahmady IM, Hasan K, Alawadhi H, Lee H, Han C, Mohamed AA. Surface Modification of Magnetite with Carboxyl Arylated Gold Nanoparticles for Capture and Removal of Bacteria. Inorg Chem 2025; 64:4555-4570. [PMID: 40014457 DOI: 10.1021/acs.inorgchem.4c05588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
This study presents a novel synthesis method for fabricating magnetic-plasmonic Fe3O4@CS-AuNPs nanocomposite utilizing aryldiazonium gold(III) salts. The low reduction potential of aryldiazonium gold salts enables their spontaneous reduction on the surface of Fe3O4 NPs stabilized with chitosan (CS), as CS facilitates the electron transfer process. The Fe3O4@CS-AuNPs nanocomposite exhibited gold plasmon peaks at 525 nm in UV-vis spectra and demonstrated long shelf life in an aqueous solution, with a ζ-potential of -42.8 mV. XPS revealed the complete reduction of gold(III) supported by the Au 4f peak for Fe3O4@CS-AuNPs. The increased Fe(II) ratio in XPS suggests a green reduction, where chitosan reduced Au(III) to Au(0). HR-TEM images demonstrated that Fe3O4@CS-AuNPs have an average nanoparticle size of 17.0 ± 3.8 nm. The high surface area of 55.15 m2/g for Fe3O4@CS-AuNPs supports their enhanced adsorption and removal of E. coli bacteria. Fe3O4@CS-AuNPs exhibited superior removal efficiencies of 100%, 99%, and 97%, outperforming Fe3O4@CS bacteria removal of 3%, 21%, and 40%. Surface modification with arylated AuNPs enhanced the adsorption and bacterial binding, enabling Fe3O4@CS-AuNPs to demonstrate high capture efficiency and bactericidal activity, eliminating viable bacteria at a minimum inhibitory concentration (MIC) of 50%. These findings highlight the potential of Fe3O4@CS-AuNPs for enhanced microbial removal.
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Affiliation(s)
- Javad B M Parambath
- Center for Advanced Materials Research, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Physics, Sathyabama Institute of Science & Technology, Chennai 600119, Tamil Nadu, India
- Department of Chemistry, Sathyabama Institute of Science & Technology, Chennai 600119, Tamil Nadu, India
| | - Kabali Vijai Anand
- Department of Physics, Sathyabama Institute of Science & Technology, Chennai 600119, Tamil Nadu, India
| | - Islam M Ahmady
- Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Kamrul Hasan
- Department of Chemistry, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Hussain Alawadhi
- Center for Advanced Materials Research, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Applied Physics & Astronomy, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Haesung Lee
- Program in Environmental and Polymer Engineering, Graduate School of INHA University, Incheon 22212, Korea
| | - Changseok Han
- Program in Environmental and Polymer Engineering, Graduate School of INHA University, Incheon 22212, Korea
- Department of Environmental Engineering, INHA University, Incheon 22212, Korea
| | - Ahmed A Mohamed
- Center for Advanced Materials Research, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
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Cheng X, Xu J, Cui Y, Liu J, Chen Y, He C, Cui L, Liu Y, Song B, Gong C, Mi P. Nanovesicles for Lipid Metabolism Reprogram-Enhanced Ferroptosis and Magnetotherapy of Refractory Tumors and Inhibiting Metastasis with Activated Innate Immunity. ACS NANO 2025; 19:7213-7230. [PMID: 39928515 DOI: 10.1021/acsnano.4c16981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/12/2025]
Abstract
Castration-resistant prostate cancer (CRPC) is an intractable disease, but approaches for eradicating primary tumors and inhibiting metastasis are limited. Considering that lipid metabolism plays key roles in ferroptosis and tumor progression and treatment resistance, here we developed a biomimetic nanovesicle (FiFe@RBM) encapsulating fatty acid synthetase inhibitors and iron oxide nanoparticles for synergistic therapy of CRPC and inhibiting the metastasis. FiFe@RBM with superior magnetic properties efficiently delivered drugs into the CRPC cancer cells, where it can release Fe ions to efficiently induce reactive oxygen species and mitochondrial dysfunction and inhibit the AKT-mTOR pathway, which synergistically causes apoptosis and enhances ferroptosis by rewired lipid metabolism through increasing polyunsaturated fatty acids (PUFAs), PUFA-enriched phosphatidylcholine (PUFA-PC), PUFA-enriched phosphatidylethanolamine (PUFA-PE), etc. By intravenous injection, the high accumulation of FiFe@RBM in PC-3 tumors enabled precision T1/T2-weighted magnetic resonance imaging-guided effective eradication of human CRPC PC-3 tumors by synergistic magnetic hyperthermia therapy (MHT) and ferroptosis, which further inhibited liver metastasis by the activated and recruited high rates of natural killer cells in the nude mice model. This work presents an effective nanovesicle strategy for reprogramming lipid metabolism to enhance ferroptosis in synergy with MHT for effectively treating refractory cancers.
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Affiliation(s)
- Xueqing Cheng
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Jinshun Xu
- Department of Ultrasound, Sichuan Cancer Hospital, Chengdu 610042, Sichuan, China
| | - Yongsheng Cui
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Jing Liu
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yuntian Chen
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Chuanshi He
- Department of Ultrasound, Sichuan Cancer Hospital, Chengdu 610042, Sichuan, China
| | - Lele Cui
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yiyao Liu
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, and School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610051, Sichuan, China
| | - Bin Song
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
- Department of Radiology, Sanya People's Hospital, Sanya 572032, Hainan, China
| | - Changyang Gong
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Peng Mi
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
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10
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Xie Q, Zhang G, Zhou D, Liu H, Yu D, Duan J. Mass production of ultrasmall Mn 3O 4 nanoparticles for glutathione responsive off-on T 1/ T 2 switching magnetic resonance imaging and tumor theranostics. RSC Adv 2025; 15:2152-2162. [PMID: 39850089 PMCID: PMC11755108 DOI: 10.1039/d4ra07224c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 12/18/2024] [Indexed: 01/25/2025] Open
Abstract
Individual theranostics with an integrated multifunction holds considerable promise for clinical application compared with multicomponent regimes. Mn3O4 nanoparticles with an ultrasmall size (4 nm) and mass production capability were developed with dual function of integrated tumor magnetic resonance imaging (MRI) and therapy. The high valence state of Mn3O4 nanocrystals enables a sensitive reaction with the glutathione (GSH) molecule and favorable decomposition ability, which further induces a unique, favorable, variable T 1 turn-off and T 2 turn-on MRI property. In addition, ultrasmall Mn3O4 nanoparticles reacted with high-level GSH in the tumor microenvironment induces responsive and enhanced variable T 1- and T 2-MRI imaging capability for accurate cancer diagnosis. Moreover, the synthesized ultrasmall Mn3O4 nanoparticles exhibit considerable ferroptosis effect towards tumor cells and excellent in vivo biocompatibility, thus indicating promising effective cancer treatment application. The developed ultrasmall Mn3O4 nanoparticles with integrated dual functions of GSH-responsive variable T 1 and T 2 MRI imaging effects and ferroptosis capability show promising potential as a candidate for tumor theranostics in clinical applications.
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Affiliation(s)
- Qinghua Xie
- State Key Laboratory of Crystal Materials, Shandong University Jinan Shandong 250100 P.R. China
- Shandong BIOBASE Biology Co., Ltd China
| | - Gaorui Zhang
- Department of Radiology, Qilu Hospital of Shandong University Jinan Shandong 250012 China
- Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University Jinan 250100 China
| | - Dawei Zhou
- Department of Radiology, Qilu Hospital of Shandong University Jinan Shandong 250012 China
- Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University Jinan 250100 China
| | - Hong Liu
- State Key Laboratory of Crystal Materials, Shandong University Jinan Shandong 250100 P.R. China
- Institute for Advanced Interdisciplinary Research, University of Jinan Jinan 250022 P. R. China
| | - Dexin Yu
- Department of Radiology, Qilu Hospital of Shandong University Jinan Shandong 250012 China
- Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University Jinan 250100 China
| | - Jiazhi Duan
- State Key Laboratory of Crystal Materials, Shandong University Jinan Shandong 250100 P.R. China
- Institute for Advanced Interdisciplinary Research, University of Jinan Jinan 250022 P. R. China
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11
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Liu H, Zhen Z, Chen F, Chen J, Chen W. Advancements in Iron Oxide Nanoparticles for Multimodal Imaging and Tumor Theranostics. Curr Med Chem 2025; 32:301-321. [PMID: 39005127 DOI: 10.2174/0109298673301359240705063544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 06/05/2024] [Accepted: 06/05/2024] [Indexed: 07/16/2024]
Abstract
The emergence of nanomedicine offers renewed promise in the diagnosis and treatment of diseases. Due to their unique physical and chemical properties, iron oxide nanoparticles (IONPs) exhibit widespread application in the diagnosis and treatment of various ailments, particularly tumors. IONPs have magnetic resonance (MR) T1/T2 imaging capabilities due to their different sizes. In addition, IONPs also have biocatalytic activity (nanozymes) and magnetocaloric effects. They are widely used in chemodynamic therapy (CDT), magnetic hyperthermia treatment (MHT), photodynamic therapy (PDT), and drug delivery. This review outlines the synthesis, modification, and biomedical applications of IONPs, emphasizing their role in enhancing diagnostic imaging (including single-mode and multimodal imaging) and their potential in cancer therapies (including chemotherapy, radiotherapy, CDT, and PDT). Furthermore, we briefly explore the challenges in the clinical application of IONPs, such as surface modification and protein adsorption, and put forward opinions on the clinical transformation of IONPs.
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Affiliation(s)
- He Liu
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- 7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhiming Zhen
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- 7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Fengxi Chen
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- 7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jiafei Chen
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- 7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Wei Chen
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- 7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
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12
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Li X, Liu Q, Wu M, Wang H, Yang J, Mu X, Zhang XD. Artificially Engineered Nanoprobes for Ultrasensitive Magnetic Resonance Imaging. Adv Healthc Mater 2025; 14:e2403099. [PMID: 39562174 DOI: 10.1002/adhm.202403099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/11/2024] [Indexed: 11/21/2024]
Abstract
Magnetic resonance imaging (MRI) is a noninvasive and radiation-free technique used for soft tissue. However, there are some limitations of the MRI modality, such as low sensitivity and poor image resolution. Artificially engineered magnetic nanoprobes have been extensively explored as a versatile platform for ultrasensitive MRI contrast agents due to their unique physiochemical characteristics and tunable magnetic properties. In this review, the emphasis is on recent progress in MRI nanoprobes with different structures and elements, including gadolinium-, iron-, manganese-based and metal-free nanoprobes. The key influencing factors and advanced engineering strategies for modulating the relaxation ratio of MRI nanoprobes are systematically condensed. Furthermore, the widespread and noninvasive visualization applications of MRI nanoprobes for real time monitoring of major organs and accurate disease diagnosing, such as cerebrovascular, ischemia, Alzheimer's disease, liver fibrosis, whole-body tumors, inflammation, as well as multi-mode imaging applications are summarized. Finally, the challenges and prospects for the future development of MRI nanoprobes are discussed, and promising strategies are specifically emphasized for improving biocompatibility, precisely engineering of optimal size, AI-driven prediction and design, and multifunctional self-assembly to enhance diagnostics. This review will provide new inspiration for artificial engineering and nanotechnology-based molecular probes for medical diagnosis and therapy with ultrasensitive MRI.
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Affiliation(s)
- Xuyan Li
- Tianjin Key Laboratory of Brain Science and Neuroengineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Qingshan Liu
- Tianjin Key Laboratory of Brain Science and Neuroengineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Menglin Wu
- Tianjin Key Laboratory of Brain Science and Neuroengineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
- Department of Radiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, China
| | - Hao Wang
- Tianjin Key Laboratory of Brain Science and Neuroengineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Jiang Yang
- School of Medicine, Sun Yat-sen University, Guangzhou, 510060, China
| | - Xiaoyu Mu
- Tianjin Key Laboratory of Brain Science and Neuroengineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
- Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Science, Tianjin University, Tianjin, 300072, China
| | - Xiao-Dong Zhang
- Tianjin Key Laboratory of Brain Science and Neuroengineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
- Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Science, Tianjin University, Tianjin, 300072, China
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13
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Solak K, Atiş M, Kasapoğlu AE, Karaman A, Mavi A. Metal Nanoparticles for Simultaneous Use in AC Magnetic Field Hyperthermia and Magnetic Resonance Imaging. J Biomed Mater Res A 2025; 113:e37817. [PMID: 39474677 DOI: 10.1002/jbm.a.37817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 09/19/2024] [Accepted: 10/07/2024] [Indexed: 12/26/2024]
Abstract
Magnetic nanoparticles (MNPs) are produced for both diagnosis and treatment due to their simultaneous availability in magnetic resonance imaging (MRI) and magnetic hyperthermia (MHT). Extensive investigations focus on developing MNPs for individual MHT or MRI applications, but the development of MNPs for theragnostic applications has received very little attention. In this study, through efficient examination of synthesis conditions such as metal precursors, reaction parameters, and solvent choices, we aimed to optimize MNP production for effective utilization for MHT and MRI simultaneously. MNPs were synthesized by thermal decomposition under 17 different conditions and deeply characterized by transmission electron microscopy (TEM), x-ray diffraction (XRD), and x-ray photoelectron spectroscopy (XPS). The heating efficiency of MNPs under an alternating current (AC) magnetic field was quantified, while MRI performance was evaluated through agar phantom experiments. Our findings highlight the crucial role of benzyl ether in metal ion reduction and size control. Metal-doped iron oxide MNPs displayed promise for MHT, whereas Mn-doped iron oxide MNPs exhibited enhanced MRI capabilities. Consequently, five engineered MNPs were considered potential candidates for further studies, demonstrating their dual ability in MRI and MHT.
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Affiliation(s)
- Kübra Solak
- Department of Nanoscience and Nanoengineering, Graduate School of Natural and Applied Sciences, Atatürk University, Erzurum, Türkiye
| | - Mustafa Atiş
- School of Medicine, Atatürk University, Erzurum, Türkiye
- School of Medicine, Ağrı İbrahim Çeçen University, Ağrı, Türkiye
| | - Ahmet Emre Kasapoğlu
- East Anatolia High Technology Application and Research Center, Atatürk University, Erzurum, Türkiye
| | - Adem Karaman
- Faculty of Medicine, Department of Radiology, Atatürk University, Erzurum, Türkiye
| | - Ahmet Mavi
- Department of Nanoscience and Nanoengineering, Graduate School of Natural and Applied Sciences, Atatürk University, Erzurum, Türkiye
- Department of Mathematics and Science Education, Kâzım Karabekir Faculty of Education, Atatürk University, Erzurum, Türkiye
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14
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Lu C, Liao S, Chen B, Xu L, Wu N, Lu D, Kang H, Zhang XB, Song G. Responsive probes for in vivo magnetic resonance imaging of nitric oxide. NATURE MATERIALS 2025; 24:133-142. [PMID: 39587281 DOI: 10.1038/s41563-024-02054-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 10/18/2024] [Indexed: 11/27/2024]
Abstract
Nitric oxide (NO), a pivotal signalling molecule, plays multifaceted roles in physiological and pathological processes, including cardiovascular and immune functions, neurotransmission and cancer progression. Nevertheless, measuring NO in vivo is challenging due to its transient nature and the complexity of the biological environment. Here we describe NO-responsive magnetic probes made of crosslinked superparamagnetic iron oxide nanoparticles tethered to a NO-sensitive cleavable linker for highly sensitive and selective NO magnetic resonance imaging in vivo. These probes enable the detection of NO at concentrations as low as 0.147 μM, allowing for the imaging and quantification of NO in mouse tumour models, studying its effects on tumour progression and immunity and assessing the response of tumour-associated macrophages to cancer immunotherapeutic agents. Additionally, they facilitate concurrent anatomical and molecular imaging of organs, helping to identify pathological alterations in the liver. Overall, these probes represent promising non-invasive tools for investigating the dose-dependent conflicting role of NO in physiological and pathophysiological processes.
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Affiliation(s)
- Chang Lu
- State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
| | - Shiyi Liao
- State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
| | - Baode Chen
- State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
| | - Li Xu
- State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
| | - Na Wu
- State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
| | - Dingyou Lu
- State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
| | - Heemin Kang
- Department of Materials Science and Engineering, Korea University, Seoul, Korea
| | - Xiao-Bing Zhang
- State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China.
| | - Guosheng Song
- State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China.
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15
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Zuo X, Wang X, Si G, Zhang D, Yu X, Guo Z, Gu N. Size-Dependent Oxygen Vacancy of Iron Oxide Nanoparticles. SMALL METHODS 2025; 9:e2400685. [PMID: 39031906 DOI: 10.1002/smtd.202400685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 06/09/2024] [Indexed: 07/22/2024]
Abstract
Prior research has highlighted the reduction of iron oxide nanoparticle (IONPs) sizes to the "ultra-small" dimension as a pivotal approach in developing T1-MRI contrast agents, and the enhancement in T1 contrast performance with the reducing size is usually attributed to the increased specific surface area and weakened magnetization. Nonetheless, as the size decreases, the variation in surface defects, particularly oxygen vacancy (VO) defects, significantly impacts the T1 imaging efficacy. In this study, the VO on IONPs is meticulously investigated through XPS, Raman, and EPR spectroscopy. As the nanoparticle size decreased, the VO concentration rose initially but subsequently declined, with the peak concentration observed in the size of 8.27 nm. Further insights gained from synchrotron XAS analysis and DFT calculations indicate that both surface tension and phase transition in IONPs contribute to alterations in the Fe─O bond length, thereby influencing the VO formation energy across varying nanoparticle sizes. The MRI tests reveal that the VO in IONPs serve as pivotal sites for the attachment of water molecules to iron ions, and IONPs with fewer VO exhibited a deterioration in T1-MRI contrast effects. This research may provide a deeper understanding of the relationship between T1 contrast performance and the size of IONPs.
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Affiliation(s)
- Xudong Zuo
- Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, P. R. China
| | - Xinyu Wang
- School of Mathematics and Physics, Jiangsu University of Technology, Changzhou, 213100, P. R. China
| | - Guangxiang Si
- Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, P. R. China
| | - Dongmei Zhang
- School of Mathematics and Physics, Jiangsu University of Technology, Changzhou, 213100, P. R. China
| | - Xiaogang Yu
- Xinyu Key Laboratory of Materials Technology and Application for Intelligent Manufacturing, School of Mechanical and Electrical Engineering, Xinyu University, Xinyu, 338004, P. R. China
| | - Zhanhang Guo
- Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, P. R. China
| | - Ning Gu
- Nanjing Key Laboratory for Cardiovascular Information and Health Engineering Medicine, Institute of Clinical Medicine, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, 210093, P. R. China
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16
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Zhang D, Zhang J, Bian X, Zhang P, Wu W, Zuo X. Iron Oxide Nanoparticle-Based T 1 Contrast Agents for Magnetic Resonance Imaging: A Review. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 15:33. [PMID: 39791792 PMCID: PMC11722098 DOI: 10.3390/nano15010033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 12/13/2024] [Accepted: 12/19/2024] [Indexed: 01/12/2025]
Abstract
This review highlights recent progress in utilizing iron oxide nanoparticles (IONPs) as a safer alternative to gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). It consolidates findings from multiple studies, discussing current T1 contrast agents (CAs), the synthesis techniques for IONPs, the theoretical principles for designing IONP-based MRI CAs, and the key factors that impact their T1 contrast efficacy, such as nanoparticle size, morphology, surface modifications, valence states, and oxygen vacancies. Furthermore, we summarize current strategies to achieve IONP-based responsive CAs, including self-assembly/disassembly and distance adjustment. This review also evaluates the biocompatibility, organ accumulation, and clearance pathways of IONPs for clinical applications. Finally, the challenges associated with the clinical translation of IONP-based T1 CAs are included.
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Affiliation(s)
- Dongmei Zhang
- School of Mathematics and Physics, Jiangsu University of Technology, Changzhou 213100, China; (D.Z.)
| | - Jing Zhang
- School of Mathematics and Physics, Jiangsu University of Technology, Changzhou 213100, China; (D.Z.)
| | - Xianglin Bian
- School of Mathematics and Physics, Jiangsu University of Technology, Changzhou 213100, China; (D.Z.)
| | - Pei Zhang
- School of Mathematics and Physics, Jiangsu University of Technology, Changzhou 213100, China; (D.Z.)
| | - Weihua Wu
- School of Mathematics and Physics, Jiangsu University of Technology, Changzhou 213100, China; (D.Z.)
| | - Xudong Zuo
- School of Mathematics and Physics, Jiangsu University of Technology, Changzhou 213100, China; (D.Z.)
- The Jiangsu Key Laboratory of Clean Energy Storage and Conversion, Jiangsu University of Technology, Changzhou 213100, China
- Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
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17
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Zhang P, Li Y, Li X, Wang Y, Lin H, Zhang N, Li W, Jing L, Jiao M, Luo X, Hou Y. Shedding light on vascular imaging: the revolutionary role of nanotechnology. J Nanobiotechnology 2024; 22:757. [PMID: 39695727 DOI: 10.1186/s12951-024-03042-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 11/28/2024] [Indexed: 12/20/2024] Open
Abstract
Vascular dysfunction, characterized by changes in anatomy, hemodynamics, and molecular expressions of vasculatures, is closely linked to the onset and development of diseases, emphasizing the importance of its detection. In clinical practice, medical imaging has been utilized as a significant tool in the assessment of vascular dysfunction, however, traditional imaging techniques still lack sufficient resolution for visualizing the complex microvascular systems. Over the past decade, with the rapid advancement of nanotechnology and the emergence of corresponding detection facilities, engineered nanomaterials offer new alternatives to traditional contrast agents. Compared with conventional small molecule counterparts, nanomaterials possess numerous advantages for vascular imaging, holding the potential to significantly advance related technologies. In this review, the latest developments in nanotechnology-assisted vascular imaging research across different imaging modalities, including contrast-enhanced magnetic resonance (MR) angiography, susceptibility-weighted imaging (SWI), and fluorescence imaging in the second near-infrared window (NIR-II) are summarized. Additionally, the advancements of preclinical and clinical studies related to these nanotechnology-enhanced vascular imaging approaches are outlined, with subsequent discussion on the current challenges and future prospects in both basic research and clinical translation.
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Affiliation(s)
- Peisen Zhang
- Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Yao Li
- Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China
| | - Xiaoqi Li
- Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China
| | - Yudong Wang
- Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China
| | - Hua Lin
- Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Ni Zhang
- Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Wenyue Li
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Lihong Jing
- Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid and Interface and Thermodynamics, CAS Research/Education Center for Excellence in Molecular Sciences, Center for Carbon Neutral Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing, 100190, China
| | - Mingxia Jiao
- Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China.
| | - Xiliang Luo
- Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China.
| | - Yi Hou
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
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18
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Calsolaro F, Garello F, Cavallari E, Magnacca G, Trukhan MV, Valsania MC, Cravotto G, Terreno E, Martina K. Amphoteric β-cyclodextrin coated iron oxide magnetic nanoparticles: new insights into synthesis and application in MRI. NANOSCALE ADVANCES 2024; 7:155-168. [PMID: 39569331 PMCID: PMC11575534 DOI: 10.1039/d4na00692e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 10/25/2024] [Indexed: 11/22/2024]
Abstract
This work presents a group of high-quality hydrophilic and negatively charged coated, iron oxide magnetic nanoparticles (MNPs) that have been prepared using a microwave-ultrasound-assisted protocol, and demonstrates the great impact that the synthetic strategy has on the resulting MNPs. The different coatings tested, including citric acid, carboxymethyl dextran and β-cyclodextrin (βCD)/citric acid have been compared and have shown good dispersibility and stability. The ability of βCD to maintain the inclusive properties of the coated MNPs has been proven as well as their cytocompatibility. An amino citrate-modified βCD is proposed and its capabilities as a flexible amphoteric adsorbing device have been studied. The NMR relaxometric properties of the coated MNPs have been investigated using field-cycling nuclear magnetic relaxation dispersion profiles. For the amino citrate-modified βCD system, the order of magnitude of the Néel relaxation time is in the typical range for superparamagnetic systems' reversal times, i.e., 10-10-10-7 s. The r d value corresponds to the physical radius of the magnetic core, suggesting that, in this particular case, the coating does not prevent the diffusive motion of water molecules, which provide the basis for potential future magnetic resonance imaging (MRI) applications.
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Affiliation(s)
- Federica Calsolaro
- Department of Drug Science and Technology, University of Turin Via P. Giuria 9 10125 Turin Italy
| | - Francesca Garello
- Department of Molecular Biotechnology and Health Sciences, University of Turin Piazza Nizza 44/bis 10126 Turin Italy
| | - Eleonora Cavallari
- Department of Molecular Biotechnology and Health Sciences, University of Turin Piazza Nizza 44/bis 10126 Turin Italy
| | - Giuliana Magnacca
- Department of Chemistry and NIS Interdepartmental Centre, University of Turin Via Pietro Giuria 7 10125 Turin Italy
| | - Mikhail V Trukhan
- Department of Drug Science and Technology, University of Turin Via P. Giuria 9 10125 Turin Italy
| | - Maria Carmen Valsania
- Department of Chemistry and NIS Interdepartmental Centre, University of Turin Via Pietro Giuria 7 10125 Turin Italy
| | - Giancarlo Cravotto
- Department of Drug Science and Technology, University of Turin Via P. Giuria 9 10125 Turin Italy
| | - Enzo Terreno
- Department of Molecular Biotechnology and Health Sciences, University of Turin Piazza Nizza 44/bis 10126 Turin Italy
| | - Katia Martina
- Department of Drug Science and Technology, University of Turin Via P. Giuria 9 10125 Turin Italy
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19
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Salehirozveh M, Dehghani P, Mijakovic I. Synthesis, Functionalization, and Biomedical Applications of Iron Oxide Nanoparticles (IONPs). J Funct Biomater 2024; 15:340. [PMID: 39590545 PMCID: PMC11595413 DOI: 10.3390/jfb15110340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 10/31/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
Iron oxide nanoparticles (IONPs) have garnered significant attention in biomedical applications due to their unique magnetic properties, biocompatibility, and versatility. This review comprehensively examines the synthesis methods, surface functionalization techniques, and diverse biomedical applications of IONPs. Various chemical and physical synthesis techniques, including coprecipitation, sol-gel processes, thermal decomposition, hydrothermal synthesis, and sonochemical routes, are discussed in detail, highlighting their advantages and limitations. Surface functionalization strategies, such as ligand exchange, encapsulation, and silanization, are explored to enhance the biocompatibility and functionality of IONPs. Special emphasis is placed on the role of IONPs in biosensing technologies, where their magnetic and optical properties enable significant advancements, including in surface-enhanced Raman scattering (SERS)-based biosensors, fluorescence biosensors, and field-effect transistor (FET) biosensors. The review explores how IONPs enhance sensitivity and selectivity in detecting biomolecules, demonstrating their potential for point-of-care diagnostics. Additionally, biomedical applications such as magnetic resonance imaging (MRI), targeted drug delivery, tissue engineering, and stem cell tracking are discussed. The challenges and future perspectives in the clinical translation of IONPs are also addressed, emphasizing the need for further research to optimize their properties and ensure safety and efficacy in medical applications. This review aims to provide a comprehensive understanding of the current state and future potential of IONPs in both biosensing and broader biomedical fields.
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Affiliation(s)
- Mostafa Salehirozveh
- Systems and Synthetic Biology Division, Department of Life Sciences, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden;
| | - Parisa Dehghani
- James Watt School of Engineering, University of Glasgow, Glasgow G12 8QQ, UK;
| | - Ivan Mijakovic
- Systems and Synthetic Biology Division, Department of Life Sciences, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden;
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark
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20
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Guedes G, Uribe KB, Martínez-Parra L, Aires A, Beraza M, Ruiz-Cabello J, Cortajarena AL. Engineering Protein-Nanoparticle Hybrids as Targeted Contrast Agents. ACS APPLIED MATERIALS & INTERFACES 2024; 16:59849-59861. [PMID: 39444371 DOI: 10.1021/acsami.4c12799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
Iron oxide nanoparticles (IONPs) have shown great promise in biomedical applications, particularly as MRI contrast agents due to their magnetic properties and biocompatibility. Although several IONPs have been approved by regulatory agencies as MRI contrast agents, their primary application as negative contrast agents limits their usage. Additionally, there is an emerging need for the development of molecular contrast agents that can specifically target biomarkers, enabling more accurate and sensitive diagnostics. To address these challenges, we exploited the engineerability of proteins to stabilize IONPs with tailored magnetic properties, creating protein-stabilized iron oxide nanoparticles (Prot-IONPs) and leveraged the chemical diversity of proteins to functionalize Prot-IONPs with targeting moieties. As a proof-of-concept, we used alendronate (Ald) to target atherosclerotic plaques in the aorta. Simple protein functionalization allowed targeting while maintaining the stability and relaxation properties of the Prot-IONPs. Prot-IONPs-Ald successfully enabled positive contrast imaging of atherosclerotic plaques in vivo in an atherosclerotic mouse model (ApoE-/- mice on a high-fat diet). This study demonstrates the potential of engineering protein-nanoparticle hybrids as versatile platforms for developing targeted in vivo MRI contrast agents.
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Affiliation(s)
- Gabriela Guedes
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Parque Tecnológico de San Sebastian Paseo Miramón 194, 20014 Donostia-San Sebastian, Spain
- Department of Biochemistry and Molecular Biology, Universidad del País Vasco UPV/EHU, 48940 Leioa, Bizkaia, Spain
| | - Kepa B Uribe
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Parque Tecnológico de San Sebastian Paseo Miramón 194, 20014 Donostia-San Sebastian, Spain
- Department of Biochemistry and Molecular Biology, Universidad del País Vasco UPV/EHU, 48940 Leioa, Bizkaia, Spain
| | - Lydia Martínez-Parra
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Parque Tecnológico de San Sebastian Paseo Miramón 194, 20014 Donostia-San Sebastian, Spain
| | - Antonio Aires
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Parque Tecnológico de San Sebastian Paseo Miramón 194, 20014 Donostia-San Sebastian, Spain
| | - Marta Beraza
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Parque Tecnológico de San Sebastian Paseo Miramón 194, 20014 Donostia-San Sebastian, Spain
| | - Jesús Ruiz-Cabello
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Parque Tecnológico de San Sebastian Paseo Miramón 194, 20014 Donostia-San Sebastian, Spain
- Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain
- Ciber Enfermedades Respiratorias (Ciberes), 28029 Madrid, Spain
- Departamento de Química en Ciencias Farmacéuticas, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Aitziber L Cortajarena
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Parque Tecnológico de San Sebastian Paseo Miramón 194, 20014 Donostia-San Sebastian, Spain
- Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain
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21
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Choi J, Kim BH. Ligands of Nanoparticles and Their Influence on the Morphologies of Nanoparticle-Based Films. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:1685. [PMID: 39453021 PMCID: PMC11510505 DOI: 10.3390/nano14201685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/18/2024] [Accepted: 10/19/2024] [Indexed: 10/26/2024]
Abstract
Nanoparticle-based thin films are increasingly being used in various applications. One of the key factors that determines the properties and performances of these films is the type of ligands attached to the nanoparticle surfaces. While long-chain surfactants, such as oleic acid, are commonly employed to stabilize nanoparticles and ensure high monodispersity, these ligands often hinder charge transport due to their insulating nature. Although thermal annealing can remove the long-chain ligands, the removal process often introduces defects such as cracks and voids. In contrast, the use of short-chain organic or inorganic ligands can minimize interparticle distance, improving film conductivity, though challenges such as incomplete ligand exchange and residual barriers remain. Polymeric ligands, especially block copolymers, can also be employed to create films with tailored porosity. This review discusses the effects of various ligand types on the morphology and performance of nanoparticle-based films, highlighting the trade-offs between conductivity, structural integrity, and functionality.
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Affiliation(s)
- Jungwook Choi
- Department of Materials Science and Engineering, Soongsil University, Seoul 06978, Republic of Korea;
| | - Byung Hyo Kim
- Department of Materials Science and Engineering, Soongsil University, Seoul 06978, Republic of Korea;
- Department of Green Chemistry and Materials Engineering, Soongsil University, Seoul 06978, Republic of Korea
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22
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Amraee A, Sarikhani A, Darvish L, Alamzadeh Z, Irajirad R, Mahdavi SR. Curcumin Coated Ultra-Small Iron Oxide Nanoparticles as T 1 Contrast Agents for Magnetic Resonance Imaging of Cancer Cells. J Biomed Phys Eng 2024; 14:447-456. [PMID: 39391281 PMCID: PMC11462277 DOI: 10.31661/jbpe.v0i0.2201-1447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 02/20/2022] [Indexed: 10/12/2024]
Abstract
Background The application of nanotechnology in the molecular diagnosis and treatment of cancer is essential. Objective This study aimed to investigate the influence of curcumin-coated ultra-small superparamagnetic iron oxide (USPIO) as a T1 contrast agent in Magnetic Resonance Imaging (MRI). Material and Methods In this experimental study, the influence of curcumin-coated USPIO (Fe3O4@C) on the diagnosis of the cancer cell line was investigated. After synthesis, characterization, and relaxation of Fe3O4@C, the contrast changes in T1-weight MRI to mouse colon carcinoma 26 cell line were evaluated in vitro. Results Fe3O4@C nanoparticles (NPs) are good at imaging; based on a relaxometry test, the r1 and r2 relaxivities of Dotarem were 3.139 and 0.603 mM-1s-1, respectively. Additionally, the r1 and r2 relaxivities of Fe3O4@C were 3.792 and 1.3 mM-1s-1, respectively, with the rate of 2.155 of r2/r1 NPs. Conclusion The NPs can be identified as a positive contrast agent with a weight of T1 in MRI. The coresh-ell Fe3O4@C NPs can be effective in cancer treatment and diagnosis because of the therapeutic effects of curcumin and the properties of USPIO.
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Affiliation(s)
- Azadeh Amraee
- Department of Medical Physics, Iran University of Medical Sciences, Tehran, Iran
| | - Abolfazl Sarikhani
- Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Leili Darvish
- Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Alamzadeh
- Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Rasoul Irajirad
- Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Rabie Mahdavi
- Department of Medical Physics, Iran University of Medical Sciences, Tehran, Iran
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23
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Zhou D, Shan S, Chen L, Li C, Wang H, Lu K, Ge J, Wang N, Afshari MJ, Zhang Y, Zeng J, Gao M. Trapped in Endosome PEGylated Ultra-Small Iron Oxide Nanoparticles Enable Extraordinarily High MR Imaging Contrast for Hepatocellular Carcinomas. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2401351. [PMID: 39162181 PMCID: PMC11497028 DOI: 10.1002/advs.202401351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 06/14/2024] [Indexed: 08/21/2024]
Abstract
The early diagnosis of hepatocellular carcinomas (HCCs) remains challenging in the clinic. Primovist-enhanced magnetic resonance imaging (MRI) aids HCC diagnosis but loses sensitivity for tumors <2 cm. Therefore, developing advanced MRI contrast agents is imperative for improving the diagnostic accuracy of HCCs in very-early-stage. To address this challenge, PEGylated ultra-small iron oxide nanoparticles (PUSIONPs) are synthesized and employed as liver-specific T1 MRI contrast agents. Intravenous delivery produces simultaneous hyperintense HCC and hypointense hepatic parenchyma signals on T1 imaging, creating an extraordinarily high tumor-to-liver contrast. Systematic studies uncover PUSIONP distribution in hepatic parenchyma, HCC lesions at the organ, tissue, cellular, and subcellular levels, revealing endosomal confinement of PUSIONP without aggregation. By mimicking such situations, the dependency of relaxometric properties on local PUSIONP concentration is investigated, emphasizing the key role of different endosomal concentrations in liver and tumor cells for high tumor-to-liver contrast and clear tumor boundaries. These findings offer exceptional imaging capabilities for early HCC diagnosis, potentially benefiting real HCC patients.
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Affiliation(s)
- Dandan Zhou
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Shanshan Shan
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Lei Chen
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Cang Li
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Hongzhao Wang
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Kuan Lu
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Jianxian Ge
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Ning Wang
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Mohammad Javad Afshari
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Yaqin Zhang
- Department of RadiologyThe Fifth Affiliated Hospital of Sun Yat‐sen UniversityZhuhai519000P. R. China
| | - Jianfeng Zeng
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
| | - Mingyuan Gao
- Center for Molecular Imaging and Nuclear MedicineState Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences (RAD‐X)Soochow UniversityCollaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSuzhou215123P. R. China
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24
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Pacheco MO, Gerzenshtein IK, Stoppel WL, Rinaldi-Ramos CM. Advances in Vascular Diagnostics using Magnetic Particle Imaging (MPI) for Blood Circulation Assessment. Adv Healthc Mater 2024; 13:e2400612. [PMID: 38879782 PMCID: PMC11442126 DOI: 10.1002/adhm.202400612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 05/11/2024] [Indexed: 06/29/2024]
Abstract
Rapid and accurate assessment of conditions characterized by altered blood flow, cardiac blood pooling, or internal bleeding is crucial for diagnosing and treating various clinical conditions. While widely used imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound offer unique diagnostic advantages, they fall short for specific indications due to limited penetration depth and prolonged acquisition times. Magnetic particle imaging (MPI), an emerging tracer-based technique, holds promise for blood circulation assessments, potentially overcoming existing limitations with reduction in background signals and high temporal and spatial resolution, below the millimeter scale. Successful imaging of blood pooling and impaired flow necessitates tracers with diverse circulation half-lives optimized for MPI signal generation. Recent MPI tracers show potential in imaging cardiovascular complications, vascular perforations, ischemia, and stroke. The impressive temporal resolution and penetration depth also position MPI as an excellent modality for real-time vessel perfusion imaging via functional MPI (fMPI). This review summarizes advancements in optimized MPI tracers for imaging blood circulation and analyzes the current state of pre-clinical applications. This work discusses perspectives on standardization required to transition MPI from a research endeavor to clinical implementation and explore additional clinical indications that may benefit from the unique capabilities of MPI.
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Affiliation(s)
| | | | - Whitney L Stoppel
- Chemical Engineering, University of Florida, Gainesville FL
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville FL
| | - Carlos M Rinaldi-Ramos
- Chemical Engineering, University of Florida, Gainesville FL
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville FL
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25
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Wang S, Li J, Chen L, Zeng J, Gao M. Fe 2+-Dominated Relaxometric Properties of Iron Oxide Nanoparticles as MRI Contrast Agents. J Phys Chem Lett 2024; 15:8861-8866. [PMID: 39169277 DOI: 10.1021/acs.jpclett.4c01876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/23/2024]
Abstract
Iron oxide nanoparticles (IONPs) have garnered significant interest as magnetic resonance imaging (MRI) contrast agents due to their exceptional magnetic properties and biocompatibility. Toward more precise diagnosis of diseases, the relaxometric properties of IONPs have become a key research focus. Despite extensive studies on structural factors such as size, morphology, surface modification, crystalline phase, and aggregation state, the correlation between the intrinsic structure and relaxometric behavior remains unclear, particularly for ultrasmall IONPs. To address this issue, we carefully compared IONPs with identical size, shape, and surface modification and found out strong correlations among the content of Fe2+ ions, oxygen vacancies, and the relaxometric properties. By optimizing the reaction system, ultrasmall IONPs showing outstanding relaxometric performance, with longitudinal relaxivity up to 9.0 mM-1 s-1 and transverse relaxivity up to 28.5 mM-1 s-1, were successfully obtained. These results underscore the pivotal role of Fe2+ in the relaxometric properties of IONP-based MRI contrast agents.
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Affiliation(s)
- Sixia Wang
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Junyan Li
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Lei Chen
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Jianfeng Zeng
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Mingyuan Gao
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
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26
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Reja S, Kumar M, Vasudevan S. Low-cost one-pot synthesis of hydrophobic and hydrophilic monodispersed iron oxide nanoparticles. NANOSCALE ADVANCES 2024; 6:3857-3864. [PMID: 39050951 PMCID: PMC11265567 DOI: 10.1039/d4na00371c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 06/12/2024] [Indexed: 07/27/2024]
Abstract
The synthesis of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) with size and shape tunability, which is also industrially scalable, remains challenging. Surface functionalization of the nanoparticles is yet another active research subject. Although a variety of inorganic and organometallic precursors have been tried, which are demanding in terms of both cost and effort, the use of iron hydroxide, a simple and cheap iron precursor, has not been explored in detail for the synthesis of SPIONs following a thermal decomposition route. Here, we outline a simple one-pot thermal decomposition route that avoids separate precursor preparation and purification steps and, consequently, is easily scalable. The method involves the alcoholic hydrolysis of a simple iron salt into iron hydroxide, which, on addition of oleic acid, forms the precursor oleate complex in situ, which is subsequently thermally decomposed to produce monodispersed SPIONS. Minor modifications allow for particle dimensions (5-20 nm) and morphology (spheroid or cuboid) to be controlled. Additionally, we explored a simple ligand exchange process for rendering the hydrophobic nanoparticles hydrophilic. Trisodium nitrilotriacetate (NTA), a readily available polycarboxylate, can efficiently transfer the oleate-coated SPIONs to water without the need for separation from the crude reaction mixture. X-ray Rietveld refinement showed that particles obtained by this method had both the magnetite and wustite phases of iron oxide present. Magnetic measurements confirm that the iron oxide particles are superparamagnetic at room temperature, with typical blocking temperatures of 183 K for the spherical and 212 K for the cuboid ones.
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Affiliation(s)
- Sohel Reja
- Department of Inorganic and Physical Chemistry, IISc Bangalore India
| | - Manoj Kumar
- Department of Inorganic and Physical Chemistry, IISc Bangalore India
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Lu Z, Yan J, Xu M, Liu J, Zeng J, Ren Y, Sun L, Zhang Y, Cao Y, Pei R. A "Dual-Key-and-Lock" MRI Contrast Agent with T 1-T 2 Switchable Function for Accurate Diagnosis of Tumors. NANO LETTERS 2024. [PMID: 39036992 DOI: 10.1021/acs.nanolett.4c02669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
Extremely small iron oxide nanoparticle (ESIONP)-based stimuli-responsive switchable MRI contrast agents (CAs) show great promise for accurate detection of tumors due to their outstanding advantages of high specificity and low background signal. However, currently developed ESIONP-based switchable CAs often suffer single-biomarker-induced responses, which lack absolute specificity to pathological tissues, potentially diminishing diagnostic accuracy. In this study, weak acidity and hypoxia, two of the most remarkable characteristics of tumors, are introduced as dual biomarker stimuli to construct an ESIONP-based switchable MRI CA (DKL-CA), with its signal switch controlled by a "dual-key-and-lock" strategy. Only when DKL-CA is exposed to a coexisting weakly acidic and hypoxic environment can monodispersed ESIONPs form nanoclusters, thereby realizing a switch from the T1 to T2 contrast. Moreover, DKL-CA exhibits favorable biosafety and the capacity for precise tumor diagnosis in tumor-bearing mice. Overall, DKL-CA paves the way for designing highly accurate ESIONP-based MRI CAs for tumor diagnosis.
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Affiliation(s)
- Zhongzhong Lu
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Jincong Yan
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Mingsheng Xu
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Jihuan Liu
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Jianxian Zeng
- Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yuxin Ren
- Department of Cardiology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Lina Sun
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Ye Zhang
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Yi Cao
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Renjun Pei
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China
- CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
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28
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Suh M, Park JY, Ko GB, Kim JY, Hwang DW, Rees L, Conway GE, Doak SH, Kang H, Lee N, Hyeon T, Lee YS, Lee DS. Optimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: biodistribution and safety profile. J Nanobiotechnology 2024; 22:419. [PMID: 39014410 PMCID: PMC11253436 DOI: 10.1186/s12951-024-02699-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 07/03/2024] [Indexed: 07/18/2024] Open
Abstract
BACKGROUND Iron oxide nanoparticles (IONPs) have been cleared by the Food and Drug Administration (FDA) for various clinical applications, such as tumor-targeted imaging, hyperthermia therapy, drug delivery, and live-cell tracking. However, the application of IONPs as T1 contrast agents has been restricted due to their high r2 values and r2/r1 ratios, which limit their effectiveness in T1 contrast enhancement. Notably, IONPs with diameters smaller than 5 nm, referred to as extremely small-sized IONPs (ESIONs), have demonstrated potential in overcoming these limitations. To advance the clinical application of ESIONs as T1 contrast agents, we have refined a scale-up process for micelle encapsulation aimed at improving the hydrophilization of ESIONs, and have carried out comprehensive in vivo biodistribution and preclinical toxicity assessments. RESULTS The optimization of the scale-up micelle-encapsulation process, specifically employing Tween60 at a concentration of 10% v/v, resulted in ESIONs that were uniformly hydrophilized, with an average size of 9.35 nm and a high purification yield. Stability tests showed that these ESIONs maintained consistent size over extended storage periods and dispersed effectively in blood and serum-mimicking environments. Relaxivity measurements indicated an r1 value of 3.43 mM- 1s- 1 and a favorable r2/r1 ratio of 5.36, suggesting their potential as T1 contrast agents. Biodistribution studies revealed that the ESIONs had extended circulation times in the bloodstream and were primarily cleared via the hepatobiliary route, with negligible renal excretion. We monitored blood clearance and organ distribution using positron emission tomography and magnetic resonance imaging (MRI). Additionally, MRI signal variations in a dose-dependent manner highlighted different behaviors at varying ESIONs concentrations, implying that optimal dosages might be specific to the intended imaging application. Preclinical safety evaluations indicated that ESIONs were tolerable in rats at doses up to 25 mg/kg. CONCLUSIONS This study effectively optimized a scale-up process for the micelle encapsulation of ESIONs, leading to the production of hydrophilic ESIONs at gram-scale levels. These optimized ESIONs showcased properties conducive to T1 contrast imaging, such as elevated r1 relaxivity and a reduced r2/r1 ratio. Biodistribution study underscored their prolonged bloodstream presence and efficient clearance through the liver and bile, without significant renal involvement. The preclinical toxicity tests affirmed the safety of the ESIONs, supporting their potential use as T1 contrast agent with versatile clinical application.
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Affiliation(s)
- Minseok Suh
- Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
| | - Ji Yong Park
- Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea
- Medical Research Center, College of Medicine, Seoul National University, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea
| | - Guen Bae Ko
- Medical Research Center, College of Medicine, Seoul National University, Seoul, Korea
- Brightonix Imaging Inc, Seoul, Korea
| | - Ji Yoon Kim
- Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea
- The Interdisciplinary Program of Cancer Biology, Seoul National University, Seoul, Korea
| | - Do Won Hwang
- Research and Development Center, THERABEST Co., Ltd., Seoul, South Korea
| | - Louis Rees
- In Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea, Wales, UK
| | - Gillian E Conway
- In Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea, Wales, UK
| | - Shareen H Doak
- In Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea, Wales, UK
| | - Hyelim Kang
- School of Advanced Materials Engineering, Kookmin University, Seoul, Korea
| | - Nohyun Lee
- School of Advanced Materials Engineering, Kookmin University, Seoul, Korea
| | - Taeghwan Hyeon
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, Korea
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, Korea
| | - Yun-Sang Lee
- Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea.
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
| | - Dong Soo Lee
- Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea.
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
- Medical Research Center, College of Medicine, Seoul National University, Seoul, Korea.
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea.
- Medical Science and Engineering, School of Convergence Science and Technology, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
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Liu M, Feng Q, Zhang H, Guo Y, Fan H. Progress in ultrasmall ferrite nanoparticles enhanced T1 magnetic resonance angiography. J Mater Chem B 2024; 12:6521-6531. [PMID: 38860874 DOI: 10.1039/d4tb00803k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2024]
Abstract
Contrast-enhanced magnetic resonance angiography (CE-MRA) plays a critical role in diagnosing and monitoring various vascular diseases. Achieving high-sensitivity detection of vascular abnormalities in CE-MRA depends on the properties of contrast agents. In contrast to clinically used gadolinium-based contrast agents (GBCAs), the new generation of ultrasmall ferrite nanoparticles-based contrast agents have high relaxivity, long blood circulation time, easy surface functionalization, and high biocompatibility, hence showing promising prospects in CE-MRA. This review aims to comprehensively summarize the advancements in ultrasmall ferrite nanoparticles-enhanced MRA for detecting vascular diseases. Additionally, this review also discusses the future clinical translational potential of ultrasmall ferrite nanoparticles-based contrast agents for vascular imaging. By investigating the current status of research and clinical applications, this review attempts to outline the progress, challenges, and future directions of using ultrasmall ferrite nanoparticles to drive the field of CE-MRA into a new frontier of accuracy and diagnostic efficacy.
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Affiliation(s)
- Minrui Liu
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi, 710127, China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 614001, China
| | - Quanqing Feng
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi, 710127, China.
| | - Huan Zhang
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi, 710127, China.
- Department of Radiology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, China
| | - Yingkun Guo
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, 614001, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 614001, China
| | - Haiming Fan
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi, 710127, China.
- Center for Nanomedicine and Engineering, School of Medicine, Northwest University, Xi'an, Shaanxi, 710127, China.
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Sarfati P, De La Taille T, Portioli C, Spanò R, Lalatonne Y, Decuzzi P, Chauvierre C. REVIEW: "ISCHEMIC STROKE: From Fibrinolysis to Functional Recovery" Nanomedicine: emerging approaches to treat ischemic stroke. Neuroscience 2024; 550:102-113. [PMID: 38056622 DOI: 10.1016/j.neuroscience.2023.11.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/27/2023] [Accepted: 11/30/2023] [Indexed: 12/08/2023]
Abstract
Stroke is responsible for 11% of all deaths worldwide, the majority of which are caused by ischemic strokes, thus making the need to urgently find safe and effective therapies. Today, these can be cured either by mechanical thrombectomy when the thrombus is accessible, or by intravenous injection of fibrinolytics. However, the latter present several limitations, such as potential severe side effects, few eligible patients and low rate of partial and full recovery. To design safer and more effective treatments, nanomedicine appeared in this medical field a few decades ago. This review will explain why nanoparticle-based therapies and imaging techniques are relevant for ischemic stroke management. Then, it will present the different nanoparticle types that have been recently developed to treat this pathology. It will also study the various targeting strategies used to bring nanoparticles to the stroke site, thereby limiting side effects and improving the therapeutic efficacy. Finally, this review will present the few clinical studies testing nanomedicine on stroke and discuss potential causes for their scarcity.
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Affiliation(s)
- Pierre Sarfati
- Université Paris Cité, Université Sorbonne Paris Nord, UMR-S U1148 INSERM, Laboratory for Vascular Translational Science (LVTS), F-75018 Paris, France
| | - Thibault De La Taille
- Université Paris Cité, Université Sorbonne Paris Nord, UMR-S U1148 INSERM, Laboratory for Vascular Translational Science (LVTS), F-75018 Paris, France
| | - Corinne Portioli
- Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
| | - Raffaele Spanò
- Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
| | - Yoann Lalatonne
- Université Paris Cité, Université Sorbonne Paris Nord, UMR-S U1148 INSERM, Laboratory for Vascular Translational Science (LVTS), F-75018 Paris, France; Département de Biophysique et de Médecine Nucléaire, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, F-93009 Bobigny, France
| | - Paolo Decuzzi
- Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
| | - Cédric Chauvierre
- Université Paris Cité, Université Sorbonne Paris Nord, UMR-S U1148 INSERM, Laboratory for Vascular Translational Science (LVTS), F-75018 Paris, France.
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31
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Forgham H, Zhu J, Huang X, Zhang C, Biggs H, Liu L, Wang YC, Fletcher N, Humphries J, Cowin G, Mardon K, Kavallaris M, Thurecht K, Davis TP, Qiao R. Multifunctional Fluoropolymer-Engineered Magnetic Nanoparticles to Facilitate Blood-Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2401340. [PMID: 38647396 PMCID: PMC11220643 DOI: 10.1002/advs.202401340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 04/01/2024] [Indexed: 04/25/2024]
Abstract
Patients with brain cancers including medulloblastoma lack treatments that are effective long-term and without side effects. In this study, a multifunctional fluoropolymer-engineered iron oxide nanoparticle gene-therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum. The blood-brain barrier (BBB) tailored system demonstrates enhanced BBB penetration, facilitates delivery of functionally active siRNA to medulloblastoma cells, and delivers a significant, almost complete block in protein expression within an in vitro extracellular acidic environment (pH 6.7) - as favored by most cancer cells. In vivo, it effectively crosses an intact BBB, provides contrast for magnetic resonance imaging (MRI), and delivers siRNA capable of slowing tumor growth without causing signs of toxicity - meaning it possesses a safe theranostic function. The pioneering methodology applied shows significant promise in the advancement of brain and tumor microenvironment-focused MRI-siRNA theranostics for the better treatment and diagnosis of medulloblastoma.
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Affiliation(s)
- Helen Forgham
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Jiayuan Zhu
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Xumin Huang
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Cheng Zhang
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
- National Imaging FacilityCentre for Advanced ImagingThe University of QueenslandSt LuciaQueensland4072Australia
| | - Heather Biggs
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Liwei Liu
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Yi Cheng Wang
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Nicholas Fletcher
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
- National Imaging FacilityCentre for Advanced ImagingThe University of QueenslandSt LuciaQueensland4072Australia
- ARC Training Centre for Innovation in Biomedical Imaging TechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - James Humphries
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
- National Imaging FacilityCentre for Advanced ImagingThe University of QueenslandSt LuciaQueensland4072Australia
- ARC Training Centre for Innovation in Biomedical Imaging TechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Gary Cowin
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
- National Imaging FacilityCentre for Advanced ImagingThe University of QueenslandSt LuciaQueensland4072Australia
| | - Karine Mardon
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
- National Imaging FacilityCentre for Advanced ImagingThe University of QueenslandSt LuciaQueensland4072Australia
| | - Maria Kavallaris
- Children's Cancer InstituteLowy Cancer Research CentreUNSW SydneyKensingtonNew South Wales2052Australia
- School of Clinical MedicineFaculty of Medicine & HealthUNSW SydneyKensingtonNew South Wales2052Australia
- UNSW Australian Centre for NanomedicineFaculty of EngineeringUNSW SydneyKensingtonNew South Wales2052Australia
- UNSW RNA InstituteFaculty of ScienceUNSW SydneyKensingtonNew South Wales2052Australia
| | - Kristofer Thurecht
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
- National Imaging FacilityCentre for Advanced ImagingThe University of QueenslandSt LuciaQueensland4072Australia
- ARC Training Centre for Innovation in Biomedical Imaging TechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Thomas P. Davis
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
| | - Ruirui Qiao
- Australian Institute of Bioengineering & NanotechnologyThe University of QueenslandSt LuciaQueensland4072Australia
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32
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Wang J, Fan X, Han X, Lv K, Zhao Y, Zhao Z, Zhao D. Ultrasmall Inorganic Mesoporous Nanoparticles: Preparation, Functionalization, and Application. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2312374. [PMID: 38686777 DOI: 10.1002/adma.202312374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 04/10/2024] [Indexed: 05/02/2024]
Abstract
Ultrasmall mesoporous nanoparticles (<50 nm), a unique porous nanomaterial, have been widely studied in many fields in the last decade owing to the abundant advantages, involving rich mesopores, low density, high surface area, numerous reaction sites, large cavity space, ultrasmall size, etc. This paper presents a review of recent advances in the preparation, functionalization, and applications of ultrasmall inorganic mesoporous nanoparticles for the first time. The soft monomicelles-directed method, in contrast to the hard-template and template-free methods, is more flexible in the synthesis of mesoporous nanoparticles. This is because the amphiphilic micelle has tunable functional blocks, controlled molecule masses, configurations and mesostructures. Focus on the soft micelle directing method, monomicelles could be classified into four types, i.e., the Pluronic-type block copolymer monomicelles, laboratory-synthesized amphiphilic block copolymers monomicelles, the single-molecule star-shaped block copolymer monomicelles, and the small-molecule anionic/cationic surfactant monomicelles. This paper also reviews the functionalization of the inner mesopores and the outer surfaces, which includes constructing the yolkshell structures (encapsulated nanoparticles), anchoring the active components packed on the shell and building an asymmetric Janus architecture. Then, several representative applications, involving catalysis, energy storage, and biomedicines are presented. Finally, the prospects and challenges of controlled synthesis and large-scale applications of ultrasmall mesoporous nanoparticles in the future are foreseen.
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Affiliation(s)
- Jie Wang
- College of Energy Materials and Chemistry, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010070, China
| | - Xiankai Fan
- College of Energy Materials and Chemistry, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010070, China
| | - Xiao Han
- College of Energy Materials and Chemistry, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010070, China
| | - Kangle Lv
- College of Resources and Environment, South-Central Minzu University, Wuhan, 430074, China
| | - Yujuan Zhao
- College of Energy Materials and Chemistry, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010070, China
| | - Zaiwang Zhao
- College of Energy Materials and Chemistry, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010070, China
| | - Dongyuan Zhao
- College of Energy Materials and Chemistry, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010070, China
- College of Chemistry and Materials, Department of Chemistry, Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, China
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33
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Du H, Wang Q, Zhang B, Liang Z, Huang C, Shi D, Li F, Ling D. Structural Defect-Enabled Magnetic Neutrality Nanoprobes for Ultra-High-Field Magnetic Resonance Imaging of Isolated Tumor Cells in Vivo. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2401538. [PMID: 38738793 DOI: 10.1002/adma.202401538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/12/2024] [Indexed: 05/14/2024]
Abstract
The identification of metastasis "seeds," isolated tumor cells (ITCs), is of paramount importance for the prognosis and tailored treatment of metastatic diseases. The conventional approach to clinical ITCs diagnosis through invasive biopsies is encumbered by the inherent risks of overdiagnosis and overtreatment. This underscores the pressing need for noninvasive ITCs detection methods that provide histopathological-level insights. Recent advancements in ultra-high-field (UHF) magnetic resonance imaging (MRI) have ignited hope for the revelation of minute lesions, including the elusive ITCs. Nevertheless, currently available MRI contrast agents are susceptible to magnetization-induced strong T2-decaying effects under UHF conditions, which compromises T1 MRI capability and further impedes the precise imaging of small lesions. Herein, this study reports a structural defect-enabled magnetic neutrality nanoprobe (MNN) distinguished by its paramagnetic properties featuring an exceptionally low magnetic susceptibility through atomic modulation, rendering it almost nonmagnetic. This unique characteristic effectively mitigates T2-decaying effect while concurrently enhancing UHF T1 contrast. Under 9 T MRI, the MNN demonstrates an unprecedentedly low r2/r1 value (≈1.06), enabling noninvasive visualization of ITCs with an exceptional detection threshold of ≈0.16 mm. These high-performance MNNs unveil the domain of hitherto undetectable minute lesions, representing a significant advancement in UHF-MRI for diagnostic purposes and fostering comprehensive metastasis research.
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Affiliation(s)
- Hui Du
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Qiyue Wang
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China
- World Laureates Association (WLA) Laboratories, Shanghai, 201203, China
| | - Bo Zhang
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China
- World Laureates Association (WLA) Laboratories, Shanghai, 201203, China
| | - Zeyu Liang
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China
| | - Canyu Huang
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Dao Shi
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Fangyuan Li
- World Laureates Association (WLA) Laboratories, Shanghai, 201203, China
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China
- Songjiang Research Institute, Songjiang Hospital, Shanghai Key Laboratory of Emotions and Affective Disorder, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, 310009, China
| | - Daishun Ling
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China
- World Laureates Association (WLA) Laboratories, Shanghai, 201203, China
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, 310009, China
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Liang Z, Xie S, Wang Q, Zhang B, Xiao L, Wang C, Liu X, Chen Y, Yang S, Du H, Qian Y, Ling D, Wu L, Li F. Ligand-Induced Atomically Segregation-Tunable Alloy Nanoprobes for Enhanced Magnetic Resonance Imaging. ACS NANO 2024; 18:15249-15260. [PMID: 38818704 DOI: 10.1021/acsnano.4c03999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2024]
Abstract
Bimetallic iron-noble metal alloy nanoparticles have emerged as promising contrast agents for magnetic resonance imaging (MRI) due to their biocompatibility and facile control over the element distribution. However, the inherent surface energy discrepancy between iron and noble metal often leads to Fe atom segregation within the nanoparticle, resulting in limited iron-water molecule interactions and, consequently, diminished relaxometric performance. In this study, we present the development of a class of ligand-induced atomically segregation-tunable alloy nanoprobes (STAN) composed of bimetallic iron-gold nanoparticles. By manipulating the oxidation state of Fe on the particle surface through varying molar ratios of oleic acid and oleylamine ligands, we successfully achieve surface Fe enrichment. Under the application of a 9 T MRI system, the optimized STAN formulation, characterized by a surface Fe content of 60.1 at %, exhibits an impressive r1 value of 2.28 mM-1·s-1, along with a low r2/r1 ratio of 6.2. This exceptional performance allows for the clear visualization of hepatic tumors as small as 0.7 mm in diameter in vivo, highlighting the immense potential of STAN as a next-generation contrast agent for highly sensitive MR imaging.
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Affiliation(s)
- Zeyu Liang
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Shangzhi Xie
- Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Qiyue Wang
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Bo Zhang
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200240, China
- World Laureates Association (WLA) Laboratories, Shanghai 201203, China
| | - Lin Xiao
- Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Chenhan Wang
- Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xun Liu
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Ying Chen
- Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Shengfei Yang
- Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Hui Du
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Yufan Qian
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Daishun Ling
- Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200240, China
- World Laureates Association (WLA) Laboratories, Shanghai 201203, China
| | - Lianming Wu
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Fangyuan Li
- Songjiang Institute and Songjiang Hospital, Shanghai Key Laboratory of Emotions and Affective Disorders (LEAD), Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- World Laureates Association (WLA) Laboratories, Shanghai 201203, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China
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Lyu Z, Kou Y, Fu Y, Xie Y, Yang B, Zhu H, Tian J. Comparative transcriptomics revealed neurodevelopmental impairments and ferroptosis induced by extremely small iron oxide nanoparticles. Front Genet 2024; 15:1402771. [PMID: 38826799 PMCID: PMC11140123 DOI: 10.3389/fgene.2024.1402771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 04/22/2024] [Indexed: 06/04/2024] Open
Abstract
Iron oxide nanoparticles are a type of nanomaterial composed of iron oxide (Fe3O4 or Fe2O3) and have a wide range of applications in magnetic resonance imaging. Compared to iron oxide nanoparticles, extremely small iron oxide nanoparticles (ESIONPs) (∼3 nm in diameter) can improve the imaging performance due to a smaller size. However, there are currently no reports on the potential toxic effects of ESIONPs on the human body. In this study, we applied ESIONPs to a zebrafish model and performed weighted gene co-expression network analysis (WGCNA) on differentially expressed genes (DEGs) in zebrafish embryos of 48 hpf, 72 hpf, 96 hpf, and 120 hpf using RNA-seq technology. The key hub genes related to neurotoxicity and ferroptosis were identified, and further experiments also demonstrated that ESIONPs impaired the neuronal and muscle development of zebrafish, and induced ferroptosis, leading to oxidative stress, cell apoptosis, and inflammatory response. Here, for the first time, we analyzed the potential toxic effects of ESIONPs through WGCNA. Our studies indicate that ESIONPs might have neurotoxicity and could induce ferroptosis, while abnormal accumulation of iron ions might increase the risk of early degenerative neurological diseases.
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Affiliation(s)
- Zhaojie Lyu
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China
- Center for Automated and Innovative Drug Discovery, School of Medicine, Northwest University, Xi’an, China
| | - Yao Kou
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China
| | - Yao Fu
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China
| | - Yuxuan Xie
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China
| | - Bo Yang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China
| | - Hongjie Zhu
- Center for Automated and Innovative Drug Discovery, School of Medicine, Northwest University, Xi’an, China
| | - Jing Tian
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China
- Center for Automated and Innovative Drug Discovery, School of Medicine, Northwest University, Xi’an, China
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36
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Dong Y, Wang J, Zhou T, Pan J, Wang X, Sun SK. Ultrasmall catechol-PEG-anchored ferrite nanoparticles for highly sensitive magnetic resonance angiography. Biomater Sci 2024; 12:2743-2754. [PMID: 38639493 DOI: 10.1039/d3bm02074f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2024]
Abstract
Highly sensitive iron oxide nanoparticles with stable, safe and efficient surface functionalization, as potential substitutes for gadolinium-based contrast agents (GBCAs) with increasing biosafety concerns, exhibit great potential for high-performance magnetic resonance angiography (MRA). Herein, we developed ultrasmall catechol-PEG-anchored ferrite nanoparticles (PEG-UMFNPs) for highly sensitive MRA. The obtained nanoprobe has a high T1 relaxivity value (7.2 mM-1 s-1) due to its ultrasmall size and Mn doping. It has a suitable hydrodynamic size of 20 nm, which prevents rapid vascular extravasation and renal clearance and prolongs its blood circulation time. In vivo MRA at 3.0 T using the nanoprobe shows that the arteries and veins of rats, even blood vessels as small as 0.32 mm, are distinctly visible, and the contrast enhancement can last for at least 1 h. In addition, due to the outstanding contrast enhancement and long circulation time, the stenosis and recanalization process of the rat's carotid artery can be continuously monitored with a single injection of the nanoprobe. Our study indicates that PEG-UMFNPs are outstanding MR imaging nanoprobes that can be used to diagnose vascular diseases without the biosafety issues of GBCAs.
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Affiliation(s)
- Yanzhi Dong
- School of Medical Imaging, Tianjin Medical University, Tianjin 300203, China.
| | - Jiaojiao Wang
- Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Ting Zhou
- School of Medical Imaging, Tianjin Medical University, Tianjin 300203, China.
| | - Jinbing Pan
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xu Wang
- Tianjin Key Laboratory of Technologies Enabling Development on Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China
| | - Shao-Kai Sun
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
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Rhakho N, Saxena M, Pradhan NR, H Jadhav A, Altaee A, Samal AK. Transformative Dynamics: Self-Assembly of Iron Oxide Hydroxide Nanorods into Iron Oxide Microcubes for Enhanced Perfluoroalkyl Substance Remediation. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2024; 40:10184-10194. [PMID: 38699923 DOI: 10.1021/acs.langmuir.4c00472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
We report the controlled synthesis of iron oxide microcubes (IOMCs) through the self-assembly arrays of ferric oxide hydroxide nanorods (NRs). The formation of IOMCs involves a complex interplay of nucleation, self-assembly, and growth mechanisms influenced by time, thermal treatment, and surfactant dynamics. The self-assembly of vertically aligned NRs into IOMCs is controlled by dynamic magnetism properties and capping agents like cetyltrimethylammonium bromide (CTAB), whose concentration and temperature modulation dictate growth kinetics and structural uniformity. These controlled structural growths were obtained via a hydrothermal process at 120 °C at various intervals of 8, 16, 24, and 32 h in the presence of CTAB as the capping agent. In this hydrothermal method, the formation of vertically oriented NR arrays was observed without the presence of ligands, binders, harsh drying techniques, and solvent evaporation. The formation of the self-assembly of NRs to IOMCs is obtained with an increase in saturated magnetization to attain the most stable state. The synthesized IOMCs have a uniform size, quasi-shape, and excellent dispersion. Due to its excellent magnetic and catalytic properties, IOMCs were employed to remove the various emerging pollutants known as per- and polyfluorinated substances (PFAS). Various microscopic and spectroscopic techniques were employed for the characterization and interaction studies of IOMCs with various PFAS. The interaction between IOMCs and perfluoroalkyl substances (PFAS) was investigated, revealing strong adsorption tendencies facilitated by electrostatic interactions, as evidenced by UV-vis and FT-IR spectroscopic studies. Furthermore, the higher magnetic and positive surface charge of IOMCs is responsible for an effective remediation eliminating any secondary pollution with ease of recovery after the sorption interaction studies, thereby making it practically worthwhile.
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Affiliation(s)
- Novuhulu Rhakho
- Centre for Nano and Material Science, JAIN (Deemed-to-be University), Jain Global Campus, Bangalore 562112, India
| | - Manav Saxena
- Centre for Nano and Material Science, JAIN (Deemed-to-be University), Jain Global Campus, Bangalore 562112, India
| | - Nihar R Pradhan
- Department of Chemistry, Physics and Atmospheric Sciences, Jackson State University, 1400 John R. Lynch Street, Jackson, Mississippi 39217, United States
| | - Arvind H Jadhav
- Centre for Nano and Material Science, JAIN (Deemed-to-be University), Jain Global Campus, Bangalore 562112, India
| | - Ali Altaee
- Centre for Green Technology, School of Civil and Environmental Engineering, University of Technology Sydney, 15 Broadway, Sydney, NSW 2007, Australia
| | - Akshaya K Samal
- Centre for Nano and Material Science, JAIN (Deemed-to-be University), Jain Global Campus, Bangalore 562112, India
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38
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Chen C, Huang B, Zhang R, Sun C, Chen L, Ge J, Zhou D, Li Y, Wu S, Qian Z, Zeng J, Gao M. Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging. J Nanobiotechnology 2024; 22:245. [PMID: 38735921 PMCID: PMC11089712 DOI: 10.1186/s12951-024-02516-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 05/01/2024] [Indexed: 05/14/2024] Open
Abstract
BACKGROUND The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape. RESULTS In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments. CONCLUSIONS We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.
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Affiliation(s)
- Can Chen
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Baoxing Huang
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Ruru Zhang
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Chaoping Sun
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Lei Chen
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Jianxian Ge
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Dandan Zhou
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Yueping Li
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Shuwang Wu
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China
| | - Zhiyuan Qian
- Clinical Translation Center of State Key Lab, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China
| | - Jianfeng Zeng
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
| | - Mingyuan Gao
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
- Clinical Translation Center of State Key Lab, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
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Xie Q, Wang X, Zhang G, Zhou D, Zhao Y, Liu H, Duan J, Yu D, Sang Y. Ultrasmall Fe 3O 4 nanoparticles self-assembly induced dual-mode T 1/T 2-weighted magnetic resonance imaging and enhanced tumor synergetic theranostics. Sci Rep 2024; 14:10646. [PMID: 38724530 PMCID: PMC11082189 DOI: 10.1038/s41598-024-59525-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024] Open
Abstract
Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe3O4 nanoclusters were developed for tumor-targeted dual-mode T1/T2-weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe3O4 nanoclusters synthesized by facilely modifying ultrasmall Fe3O4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe3O4 nanoclusters shows excellent dual-mode T1 and T2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe3O4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe3O4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.
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Affiliation(s)
- Qinghua Xie
- State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, China
- Shandong BIOBASE Biology Co., Ltd, Jinan, 250000, Shandong, China
| | - Xuemei Wang
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China
- Qingzhou Peoples`S Hospital, Qingzhou, 262500, Shandong, China
| | - Gaorui Zhang
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China
- Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University, Jinan, 250100, China
| | - Dawei Zhou
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China
- Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University, Jinan, 250100, China
| | - Yuxuan Zhao
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China
- Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University, Jinan, 250100, China
| | - Hong Liu
- State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, China
| | - Jiazhi Duan
- State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, China.
| | - Dexin Yu
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
- Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University, Jinan, 250100, China.
| | - Yuanhua Sang
- State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, China.
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40
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Yang M, Kasbe P, Bu J, Xu W. Scalable solid-state synthesis of 2D transition metal oxide/graphene hybrid materials and their utilization for microsupercapacitors. NANOSCALE 2024; 16:8390-8400. [PMID: 38602122 DOI: 10.1039/d4nr00587b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Abstract
Two-dimensional metal oxide (MO) nanostructures have unique properties compared with their bulk or 0D and 1D (nanoparticle and nanowire) counterparts. Their abundant surface area and atomically thin 2D structure are advantageous for their applications in catalysis and energy, as well as integration with 2D layered materials such as graphene and reduced graphene oxide (rGO). However, fast and scalable synthesis of 2D MOs and their nanocomposites remains challenging. Here, we developed a microwave-assisted solid-state synthesis method for the scalable generation of 2D MOs and 2D MO/rGO nanocomposites with tunable structure and composition. The structures and properties of 2D Fe2O3 and 2D ZnO as well as their nanocomposites with rGO were systematically investigated. The excellent electrochemical properties of such 2D MO/rGO nanocomposites also enable us to use them as electrode materials to fabricate microsupercapacitors. This work provides new insights into the scalable and solid-state synthesis of 2D nanocomposites and their potential applications in catalysis, energy conversion and storage.
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Affiliation(s)
- Muxuan Yang
- School of Polymer Science and Polymer Engineering, The University of Akron, Akron, OH 44325, USA.
| | - Pratik Kasbe
- School of Polymer Science and Polymer Engineering, The University of Akron, Akron, OH 44325, USA.
| | - Jinyu Bu
- School of Polymer Science and Polymer Engineering, The University of Akron, Akron, OH 44325, USA.
| | - Weinan Xu
- School of Polymer Science and Polymer Engineering, The University of Akron, Akron, OH 44325, USA.
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41
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Zhou T, Dong Y, Wang X, Liu R, Cheng R, Pan J, Zhang X, Sun SK. Highly Sensitive Early Diagnosis of Kidney Damage Using Renal Clearable Zwitterion-Coated Ferrite Nanoprobe via Magnetic Resonance Imaging In Vivo. Adv Healthc Mater 2024; 13:e2304577. [PMID: 38278515 DOI: 10.1002/adhm.202304577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Indexed: 01/28/2024]
Abstract
Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T1 relaxivity (12.52 mm-1s-1), a small hydrodynamic size (6.43 nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.
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Affiliation(s)
- Ting Zhou
- School of Medical Imaging, Tianjin Medical University, Tianjin, 300203, China
| | - Yanzhi Dong
- School of Medical Imaging, Tianjin Medical University, Tianjin, 300203, China
| | - Xiaoyi Wang
- Department of Radiology and Ultrasound, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China
| | - Ruxia Liu
- Department of Rehabilitation, School of Medical Technology, Tianjin Medical University, Tianjin, 300203, China
| | - Ran Cheng
- School of Medical Imaging, Tianjin Medical University, Tianjin, 300203, China
| | - Jinbin Pan
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging, Tianjin Medical, University General Hospital, Tianjin, 300052, China
| | - Xuejun Zhang
- School of Medical Imaging, Tianjin Medical University, Tianjin, 300203, China
| | - Shao-Kai Sun
- School of Medical Imaging, Tianjin Medical University, Tianjin, 300203, China
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42
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Lee S, Byun A, Jo J, Suh JM, Yoo J, Lim MH, Kim JW, Shin TH, Choi JS. Ultrasmall Mn-doped iron oxide nanoparticles with dual hepatobiliary and renal clearances for T1 MR liver imaging. NANOSCALE ADVANCES 2024; 6:2177-2184. [PMID: 38633040 PMCID: PMC11019488 DOI: 10.1039/d3na00933e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 03/03/2024] [Indexed: 04/19/2024]
Abstract
Although magnetic nanoparticles demonstrate significant potential as magnetic resonance imaging (MRI) contrast agents, their negative contrasts, liver accumulation, and limited excretion hinder their application. Herein, we developed ultrasmall Mn-doped iron oxide nanoparticles (UMIOs) with distinct advantages as T1 MRI contrast agents. Exceptionally small particle sizes (ca. 2 nm) and magnetization values (5 emu gMn+Fe-1) of UMIOs provided optimal T1 contrast effects with an ideally low r2/r1 value of ∼1. Furthermore, the use of Mn as a dopant facilitated hepatocyte uptake of the particles, allowing liver imaging. In animal studies, UMIOs exhibited significantly enhanced contrasts for sequential T1 imaging of blood vessels and the liver, distinguishing them from conventional magnetic nanoparticles. UMIOs were systematically cleared via dual hepatobiliary and renal excretion pathways, highlighting their safety profile. These characteristics imply substantial potential of UMIOs as T1 contrast agents for the accurate diagnosis of liver diseases.
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Affiliation(s)
- Sanghoon Lee
- Department of Chemical and Biological Engineering, Hanbat National University Daejeon 34158 Korea
| | - Arim Byun
- Department of Chemical and Biological Engineering, Hanbat National University Daejeon 34158 Korea
| | - Juhee Jo
- Inventera Inc. Seoul 06588 Republic of Korea
| | - Jong-Min Suh
- Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Korea
| | - Jeasang Yoo
- Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Korea
| | - Mi Hee Lim
- Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Korea
| | - Ji-Wook Kim
- Inventera Inc. Seoul 06588 Republic of Korea
| | | | - Jin-Sil Choi
- Department of Chemical and Biological Engineering, Hanbat National University Daejeon 34158 Korea
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43
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Liu H, Yan W, Ma C, Zhang K, Li K, Jin R, Xu H, Xu R, Tong J, Yang Z, Guo Y. Early detection of cardiac fibrosis in diabetic mice by targeting myocardiopathy and matrix metalloproteinase 2. Acta Biomater 2024; 176:367-378. [PMID: 38244659 DOI: 10.1016/j.actbio.2024.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 01/10/2024] [Accepted: 01/11/2024] [Indexed: 01/22/2024]
Abstract
Early detection of myocardial fibrosis in diabetic cardiomyopathy (DCM) has significant clinical implications for diabetes management. In this study, we identified matrix metalloproteinase 2 (MMP2) as a potential biomarker for early fibrosis detection. Based on this finding, we designed a dual-targeting nanoparticle CHP-SPIO-ab MMP2 to specifically target myocardiopathy and MMP2, enabling sensitive fibrosis detection using magnetic resonance imaging (MRI). Our results demonstrate that collagen hyperplasia (early fiber formation) begins to develop in diabetic mice at 12 weeks old, with observable fibrosis occurring at 16 weeks old. Additionally, MMP2 expression significantly up-regulates around collagen starting from 12 weeks of age. T2 MRI analysis revealed significant T2% enhancement in the hearts of 12-week-old diabetic mice following administration of the CHP-SPIO-ab MMP2 probe, indicating noninvasive detection of fiber formation. Furthermore, after fibrosis treatment, a reduction in T2% signal was observed in the hearts of 16-week-old diabetic mice. These findings were supported by Sirius red and Prussian blue staining techniques. Overall, our study presents a promising strategy for early identification of myocardial fibrosis. STATEMENT OF SIGNIFICANCE: Myocardial damage typically exhibits irreversibility, underscoring the paramount importance of early fibrosis diagnosis. However, the clinical used T1 mapping for fibrosis detection still exhibits limitations in terms of sensitivity. Therefore, it is imperative to develop highly sensitive strategies for early cardiac fibrosis detection. Here, we investigated the development of myocardial fibrosis in diabetic mice, and designed a highly sensitive probe that specifically targets cardiomyopathy and high expression of MMP2 for the early diagnosis of fibrosis. The probe enables non-invasive detection of abnormalities through MRI imaging as soon as fiber deposition appear, which can be detected earlier than T1 mapping. This advancement holds great potential for clinical diagnosis of myocardial fibrosis using cardiac magnetic resonance.
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Affiliation(s)
- Hanrui Liu
- Key Laboratory of Obstet & Gynecol & Pediat Dis, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Weifeng Yan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Chengyong Ma
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Kun Zhang
- Key Laboratory of Obstet & Gynecol & Pediat Dis, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Kuan Li
- Key Laboratory of Obstet & Gynecol & Pediat Dis, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Rongrong Jin
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Huayan Xu
- Key Laboratory of Obstet & Gynecol & Pediat Dis, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Rong Xu
- Key Laboratory of Obstet & Gynecol & Pediat Dis, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jiyu Tong
- Department of Pediatrics and Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, China
| | - Zhigang Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
| | - Yingkun Guo
- Key Laboratory of Obstet & Gynecol & Pediat Dis, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
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Ma Z, Yang K, Li D, Liu H, Hui S, Jiang Y, Li S, Li Y, Yang W, Wu H, Hou Y. The Electron Migration Polarization Boosting Electromagnetic Wave Absorption Based on Ce Atoms Modulated yolk@shell Fe x N@NGC. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024:e2314233. [PMID: 38380795 DOI: 10.1002/adma.202314233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/19/2024] [Indexed: 02/22/2024]
Abstract
The electron migration polarization is considered as a promising approach to optimize electromagnetic waves (EMW) dissipation. However, it is still difficult to realize well-controlled electron migration and elucidate the related EMW loss mechanisms for current researches. Herein, a novel Fex N@NGC/Ce system to construct an effective electron migration model based on the electron leaps among the 4f/5d/6s orbitals of Ce ions is explored. In Fe4 N@NGC/CeSA+Cs+NPs , Ce single-atoms (SA) mainly represent a +3 valence state, which can feed the electrons to Ce4+ of clusters (Cs) and CeO2 nanoparticles (NPs) through a conductive network under EMW, leading to the electron migration polarization. Such electron migration loss combined with excellent magnetic loss provided by Fe4 N core, results in the optimal EMW attenuation performance with a minimum reflection loss exceeds -85.1 dB and a broadened absorption bandwidth up to 7.5 GHz at 1.5 mm. This study clarifies the in-depth relationship between electron migration polarization and EMW dissipation, providing profound insights into developing well-coordinated magnetic-dielectric nanocomposites for EMW absorption engineering.
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Affiliation(s)
- Zhenhui Ma
- Department of Physics, Beijing Technology and Business University, Beijing, 100048, China
| | - Ke Yang
- Department of Physics, Beijing Technology and Business University, Beijing, 100048, China
| | - Da Li
- School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Hu Liu
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, China
| | - Shengchong Hui
- MOE Key Laboratory of Material Physics and Chemistry under Extraordinary, School of Physical Science and Technology Northwestern Polytechnical University, Xi'an, 710072, China
| | - Yuying Jiang
- Department of Physics, Beijing Technology and Business University, Beijing, 100048, China
| | - Siyuan Li
- State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Beijing, 102249, China
| | - Yiming Li
- Department of Physics, Beijing Technology and Business University, Beijing, 100048, China
| | - Wang Yang
- State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Beijing, 102249, China
| | - Hongjing Wu
- MOE Key Laboratory of Material Physics and Chemistry under Extraordinary, School of Physical Science and Technology Northwestern Polytechnical University, Xi'an, 710072, China
| | - Yanglong Hou
- Beijing Key Laboratory for Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Peking University, Beijing, 100871, China
- School of Materials, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, 518107, China
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45
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Wang L, Li N, Wang W, Mei A, Shao J, Wang W, Dong X. Benzobisthiadiazole-Based Small Molecular Near-Infrared-II Fluorophores: From Molecular Engineering to Nanophototheranostics. ACS NANO 2024; 18:4683-4703. [PMID: 38295152 DOI: 10.1021/acsnano.3c12316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Abstract
Organic fluorescent molecules with emission in the second near-infrared (NIR-II) biological window have aroused increasing investigation in cancer phototheranostics. Among these studies, Benzobisthiadiazole (BBT), with high electron affinity, is widely utilized as the electron acceptor in constructing donor-acceptor-donor (D-A-D) structured fluorophores with intensive near-infrared (NIR) absorption and NIR-II fluorescence. Until now, numerous BBT-based NIR-II dyes have been employed in tumor phototheranostics due to their exceptional structure tunability, biocompatibility, and photophysical properties. This review systematically overviews the research progress of BBT-based small molecular NIR-II dyes and focuses on molecule design and bioapplications. First, the molecular engineering strategies to fine-tune the photophysical properties in constructing the high-performance BBT-based NIR-II fluorophores are discussed in detail. Then, their biological applications in optical imaging and phototherapy are highlighted. Finally, the current challenges and future prospects of BBT-based NIR-II fluorescent dyes are also summarized. This review is believed to significantly promote the further progress of BBT-derived NIR-II fluorophores for cancer phototheranostics.
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Affiliation(s)
- Leichen Wang
- Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China
| | - Na Li
- Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China
| | - Weili Wang
- Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China
| | - Anqing Mei
- Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China
| | - Jinjun Shao
- Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China
| | - Wenjun Wang
- School of Physicals and Information Technology, Liaocheng University, Liaocheng 252059, China
| | - Xiaochen Dong
- Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China
- School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, China
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Bok I, Rauch B, Ashtiani A, Hai A. Direct observation of NMR transverse relaxation in nanopatterned clusters of iron oxide particles. Magn Reson Med 2024; 91:687-698. [PMID: 37867452 PMCID: PMC11489851 DOI: 10.1002/mrm.29898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 10/04/2023] [Accepted: 10/05/2023] [Indexed: 10/24/2023]
Abstract
PURPOSE We aim to verify predictions showing T2 relaxation rate of nanoparticle clusters and its dependence on spacing, size, geometry, and pulse sequence. METHODS We performed a laboratory validation study using nanopatterned arrays of iron oxide nanoparticles to precisely control cluster geometry and image diverse samples using a 4.7T MRI scanner with a T2 -weighted fast spin-echo multislice sequence. We applied denoising and normalization to regions of interest and estimated relative R2 for each relevant nanoparticle array or nanocluster array. We determined significance using an unpaired two-tailed t-test or one-way analysis of variance and performed curve fitting. RESULTS We measured a density-dependent T2 effect (p = 8.9976 × 10-20 , one-way analysis of variance) and insignificant effect of cluster anisotropy (p = 0.5924, unpaired t-test) on T2 relaxation. We found negative quadratic relationships (-0.0045[log τD ]2 -0.0655[log τD ]-2.7800) for single nanoparticles of varying sizes and for clusters (-0.0045[log τD ]2 -0.0827[log τD ]-2.3249) for diffusional correlation time τD = rp 2 /D. Clusters show positive quadratic relationships for large (3.8615 × 10-6 [dpp /rp ]2 -9.3853 × 10-5 [dpp /rp ]-2.0393) and exponential relationships for small (-2.0050[dpp /rp ]0.0010 ) clusters. Calculated R2 peak values also align well with in silico predictions (7.85 × 10-4 ms compared with 1.47 × 10-4 , 4.23 × 10-4 , and 5.02 × 10-4 ms for single iron oxide nanoparticles, 7.88 × 10-4 ms compared with 5.24 × 10-4 ms for nanoparticle clusters). CONCLUSION Our verification affirms longstanding in silico predictions and demonstrates aggregation-dependent behavior in agreement with previous Monte Carlo simulation studies.
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Affiliation(s)
- Ilhan Bok
- Department of Biomedical Engineering, University of Wisconsin–Madison, Madison, Wisconsin, USA
- Department of Electrical and Computer Engineering, University of Wisconsin – Madison, Madison, Wisconsin, USA
- Wisconsin Institute for Translational Neuroengineering (WITNe), Madison, Wisconsin, USA
| | - Beth Rauch
- Department of Medical Physics, University of Wisconsin – Madison, Madison, Wisconsin, USA
| | - Alireza Ashtiani
- Department of Biomedical Engineering, University of Wisconsin–Madison, Madison, Wisconsin, USA
| | - Aviad Hai
- Department of Biomedical Engineering, University of Wisconsin–Madison, Madison, Wisconsin, USA
- Department of Electrical and Computer Engineering, University of Wisconsin – Madison, Madison, Wisconsin, USA
- Wisconsin Institute for Translational Neuroengineering (WITNe), Madison, Wisconsin, USA
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Xu S, Zhang G, Zhang J, Liu W, Wang Y, Fu X. Advances in Brain Tumor Therapy Based on the Magnetic Nanoparticles. Int J Nanomedicine 2023; 18:7803-7823. [PMID: 38144513 PMCID: PMC10749175 DOI: 10.2147/ijn.s444319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 12/15/2023] [Indexed: 12/26/2023] Open
Abstract
Brain tumors, including primary gliomas and brain metastases, are one of the deadliest tumors because effective macromolecular antitumor drugs cannot easily penetrate the blood-brain barrier (BBB) and blood-brain tumor barrier (BTB). Magnetic nanoparticles (MNPs) are considered the most suitable nanocarriers for the delivery of brain tumor drugs because of their unique properties compared to other nanoparticles. Numerous preclinical and clinical studies have demonstrated the potential of these nanoparticles in magnetic targeting, nuclear magnetic resonance, magnetic thermal therapy, and ultrasonic hyperthermia. To further develop and optimize MNPs for the diagnosis and treatment of brain tumors, we attempt to outline recent advances in the use of MNPs to deliver drugs, with a particular focus on their efficacy in the delivery of anti-brain tumor drugs based on magnetic targeting and low-intensity focused ultrasound, magnetic resonance imaging for surgical real-time guidance, and magnetothermal and ultrasonic hyperthermia therapy. Furthermore, we summarize recent findings on the clinical application of MNPs and the research limitations that need to be addressed in clinical translation.
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Affiliation(s)
- Songbai Xu
- Department of Neurosurgery, Department of Obstetrics, Obstetrics and Gynaecology Center, the First Hospital Jilin University, Changchun, People’s Republic of China
| | - Guangxin Zhang
- Department of Endocrinology, Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, Department of Thoracic Surgery, the Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Jiaomei Zhang
- Department of Neurosurgery, Department of Obstetrics, Obstetrics and Gynaecology Center, the First Hospital Jilin University, Changchun, People’s Republic of China
| | - Wei Liu
- Department of Endocrinology, Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, Department of Thoracic Surgery, the Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Yicun Wang
- Department of Endocrinology, Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, Department of Thoracic Surgery, the Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Xiying Fu
- Department of Endocrinology, Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, Department of Thoracic Surgery, the Second Hospital of Jilin University, Changchun, People’s Republic of China
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Yang J, Yan M, Wang Z, Zhang C, Guan M, Sun Z. Optical and MRI Multimodal Tracing of Stem Cells In Vivo. Mol Imaging 2023; 2023:4223485. [PMID: 38148836 PMCID: PMC10751174 DOI: 10.1155/2023/4223485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 11/01/2023] [Accepted: 12/01/2023] [Indexed: 12/28/2023] Open
Abstract
Stem cell therapy has shown great clinical potential in oncology, injury, inflammation, and cardiovascular disease. However, due to the technical limitations of the in vivo visualization of transplanted stem cells, the therapeutic mechanisms and biosafety of stem cells in vivo are poorly defined, which limits the speed of clinical translation. The commonly used methods for the in vivo tracing of stem cells currently include optical imaging, magnetic resonance imaging (MRI), and nuclear medicine imaging. However, nuclear medicine imaging involves radioactive materials, MRI has low resolution at the cellular level, and optical imaging has poor tissue penetration in vivo. It is difficult for a single imaging method to simultaneously achieve the high penetration, high resolution, and noninvasiveness needed for in vivo imaging. However, multimodal imaging combines the advantages of different imaging modalities to determine the fate of stem cells in vivo in a multidimensional way. This review provides an overview of various multimodal imaging technologies and labeling methods commonly used for tracing stem cells, including optical imaging, MRI, and the combination of the two, while explaining the principles involved, comparing the advantages and disadvantages of different combination schemes, and discussing the challenges and prospects of human stem cell tracking techniques.
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Affiliation(s)
- Jia Yang
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China
- Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China
| | - Min Yan
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China
- Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China
| | - Zhong Wang
- Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan 650000, China
| | - Cong Zhang
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China
- Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China
| | - Miao Guan
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China
| | - Zhenglong Sun
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China
- Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China
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Gaudu N, Farr O, Ona-Nguema G, Duval S. Dissolved metal ions and mineral-liposome hybrid systems: Underlying interactions, synthesis, and characterization. Biochimie 2023; 215:100-112. [PMID: 37699473 DOI: 10.1016/j.biochi.2023.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/19/2023] [Accepted: 09/05/2023] [Indexed: 09/14/2023]
Abstract
Liposomes are versatile lipid-based vesicles with interesting physicochemical properties, making them excellent candidates for interdisciplinary applications in the medicinal, biological, and environmental sciences. The synthesis of mineral-liposome hybrid systems lends normally inert vesicles with the catalytic, magnetic, electrical, and optical properties of the integrated mineral species. Such applications require an understanding of the physicochemical interactions between organic molecules and inorganic crystal structures. This review provides an overview on these interactions and details on synthesis and characterization methods for these systems.
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Affiliation(s)
- Nil Gaudu
- Laboratoire de Bioénergétique et Ingénierie des Protéines (BIP), Aix-Marseille Université, UMR 7281 IMM-CNRS, 31 Chemin Joseph Aiguier, 13400, Marseille, France.
| | - Orion Farr
- Laboratoire de Bioénergétique et Ingénierie des Protéines (BIP), Aix-Marseille Université, UMR 7281 IMM-CNRS, 31 Chemin Joseph Aiguier, 13400, Marseille, France; Centre Interdisciplinaire des Nanosciences de Marseille (CINaM), Aix-Marseille Université, UMR 7325 CNRS, Campus de Luminy, 13288, Marseille, France
| | - Georges Ona-Nguema
- Sorbonne Université - CNRS UMR 7590 - Muséum National D'Histoire Naturelle - IRD UMR 206, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie (IMPMC), Faculté des Sciences et Ingénierie, Campus Pierre & Marie Curie, 4 Place Jussieu, F-75005, Paris, France
| | - Simon Duval
- Laboratoire de Bioénergétique et Ingénierie des Protéines (BIP), Aix-Marseille Université, UMR 7281 IMM-CNRS, 31 Chemin Joseph Aiguier, 13400, Marseille, France
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Zhang P, Li W, Liu C, Qin F, Lu Y, Qin M, Hou Y. Molecular imaging of tumour-associated pathological biomarkers with smart nanoprobe: From "Seeing" to "Measuring". EXPLORATION (BEIJING, CHINA) 2023; 3:20230070. [PMID: 38264683 PMCID: PMC10742208 DOI: 10.1002/exp.20230070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 09/18/2023] [Indexed: 01/25/2024]
Abstract
Although the extraordinary progress has been made in molecular biology, the prevention of cancer remains arduous. Most solid tumours exhibit both spatial and temporal heterogeneity, which is difficult to be mimicked in vitro. Additionally, the complex biochemical and immune features of tumour microenvironment significantly affect the tumour development. Molecular imaging aims at the exploitation of tumour-associated molecules as specific targets of customized molecular probe, thereby generating image contrast of tumour markers, and offering opportunities to non-invasively evaluate the pathological characteristics of tumours in vivo. Particularly, there are no "standard markers" as control in clinical imaging diagnosis of individuals, so the tumour pathological characteristics-responsive nanoprobe-based quantitative molecular imaging, which is able to visualize and determine the accurate content values of heterogeneous distribution of pathological molecules in solid tumours, can provide criteria for cancer diagnosis. In this context, a variety of "smart" quantitative molecular imaging nanoprobes have been designed, in order to provide feasible approaches to quantitatively visualize the tumour-associated pathological molecules in vivo. This review summarizes the recent achievements in the designs of these nanoprobes, and highlights the state-of-the-art technologies in quantitative imaging of tumour-associated pathological molecules.
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Affiliation(s)
- Peisen Zhang
- College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingChina
- Department of ChemistryUniversity of TorontoTorontoOntarioCanada
| | - Wenyue Li
- College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingChina
| | - Chuang Liu
- College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingChina
| | - Feng Qin
- Department of Neurosurgery and National Chengdu Center for Safety Evaluation of DrugsState Key Laboratory of Biotherapy/Collaborative Innovation Center for BiotherapyWest China Hospital, Sichuan UniversityChengduChina
| | - Yijie Lu
- Department of ChemistryUniversity of TorontoTorontoOntarioCanada
| | - Meng Qin
- Department of Neurosurgery and National Chengdu Center for Safety Evaluation of DrugsState Key Laboratory of Biotherapy/Collaborative Innovation Center for BiotherapyWest China Hospital, Sichuan UniversityChengduChina
| | - Yi Hou
- College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingChina
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