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1
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Reuning U, D'Amore VM, Hodivala-Dilke K, Marinelli L, Kessler H. Importance of integrin transmembrane helical interactions for antagonistic versus agonistic ligand behavior: Consequences for medical applications. Bioorg Chem 2025; 156:108193. [PMID: 39842299 DOI: 10.1016/j.bioorg.2025.108193] [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: 08/08/2024] [Revised: 11/27/2024] [Accepted: 01/17/2025] [Indexed: 01/24/2025]
Abstract
Integrins are well-characterized receptors involved in cell adhesion and signaling. With six approved drugs, they are recognized as valuable therapeutic targets. Here, we explore potential activation mechanisms that may clarify the agonist versus antagonist behavior of integrin ligands. The reorganization of the transmembrane domain (TMD) in the integrin receptor, forming homooligomers within focal adhesions, could be key to the understanding of the agonistic properties of integrin ligands at substoichiometric concentrations. This has significant implications for medical applications. While we focus on the RGD peptide-recognizing integrin subfamily, we propose that these mechanistic insights may also apply to other integrin subtypes. For application of integrin ligands in medicine it is essential to consider this mechanism and its consequences for affinity and bioavailability.
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Affiliation(s)
- Ute Reuning
- TUM University Hospital, Klinikum Rechts der Isar, School of Medicine and Health, Technical University of Munich, Department of Gynecology and Obstetrics, Clinical Research Unit, Ismaninger Strasse 22, 81675 Munich, Germany.
| | - Vincenzo Maria D'Amore
- University of Naples Federico II, UNINA-Department of Pharmacy, C.so Umberto I, 40, 80138 Naples, Italy.
| | - Kairbaan Hodivala-Dilke
- Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom.
| | - Luciana Marinelli
- University of Naples Federico II, UNINA-Department of Pharmacy, C.so Umberto I, 40, 80138 Naples, Italy.
| | - Horst Kessler
- Institute for Advanced Study, Department of Chemistry, School of Natural Sciences and Bavarian NMR Center (BNMRZ), Technical University Munich, Ernst-Otto-Fischer-Str. 2, 85748 Garching, Germany.
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2
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Delgado-Corrales BJ, Chopra V, Chauhan G. Gold nanostars and nanourchins for enhanced photothermal therapy, bioimaging, and theranostics. J Mater Chem B 2025; 13:399-428. [PMID: 39575861 DOI: 10.1039/d4tb01420k] [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: 12/06/2024]
Abstract
Photothermal therapy (PTT), a recently emerging method for eradicating tumors, utilizes hyperthermia induced by photo-absorbing materials to generate heat within cancer cells. Gold nanoparticles (AuNPs) have gained reliability for in vitro and in vivo applications in PTT due to their strong light absorbance, stability, and biocompatibility. Yet, their potential is limited by their spherical shape, impacting their size capabilities, electromagnetic enhancement effects, and localized surface plasmon resonance (LSPR). Anisotropic shapes have been tested and implemented in this treatment to overcome the limitations of spherical AuNPs. Nanostars (AuNSs) and nanourchins (AuNUs) offer unique properties, such as increased local electron density, improved catalytic activity, and an enhanced electromagnetic field, which have proven to be effective in PTT. Additionally, these shapes can easily reach the NIR-I and NIR-II window while exhibiting improved biological properties, including low cytotoxicity and high cellular uptake. This work covers the critical characteristics of AuNS and AuNUs, highlighting rough surface photothermal conversion enhancement, significantly impacting recent PTT and its synergy with other treatments. Additionally, the bioimaging and theranostic applications of these nanomaterials are discussed, highlighting their multifaceted utility in advanced cancer therapies.
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Affiliation(s)
- Beverly Jazmine Delgado-Corrales
- School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, Nuevo León, Mexico.
| | - Vianni Chopra
- School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, Nuevo León, Mexico.
| | - Gaurav Chauhan
- School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, Nuevo León, Mexico.
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3
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Paranthaman S, Hani U, Osmani RAM, Bhosale RR, Haider N. Current advances in nanoparticle-based approaches for the hepatocellular carcinoma treatment. Clin Res Hepatol Gastroenterol 2025; 49:102508. [PMID: 39613027 DOI: 10.1016/j.clinre.2024.102508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 11/18/2024] [Accepted: 11/26/2024] [Indexed: 12/01/2024]
Abstract
Hepatocellular carcinoma (HCC) is the most common form of liver (LC) with a high mortality rate, driven by risk factors including viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis. The incident of HCC increases 2-4% of the worldwide population each year which would most certainly exceed one million per year by 2025. Despite advances in our knowledge, 25% of HCC tumors have actionable mutations which demands for innovative treatments strategies. In this perspective, we are providing a comprehensive summary of nanoparticles (NPs) based therapeutic approaches for HCC. We begin with an overview of HCC, concentrating on its pathogenesis, current conventional therapies, and their limitations. Then we delve into the therapeutic application of various nanoparticles (NPs) platforms for HCC, including polymeric micelles, dendrimers, liposomes, solid-lipid nanoparticles, nanostructured lipid carriers, exosomes, niosomes, mesoporous silica nanoparticles, carbon nanotubes. Special attention is given to the application of NPs in photothermal and photodynamic treatment was also investigated, with a focus on their effectiveness in targeted cancer ablation. Additionally, the review discusses recent patents and clinical studies that demonstrate the promise of NPs-based therapies in improving HCC treatment outcomes. This article underscores the potential of NPs based technologies to address the challenges faced by traditional therapies and offers insights into future directions for HCC management.
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Affiliation(s)
- Sathishbabu Paranthaman
- Department of Cell Biology and Molecular Genetics, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Tamaka, Karnataka, 563103, India.
| | - Umme Hani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia
| | - Riyaz Ali M Osmani
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Shivarathreeshwara Nagara, Mysuru, 570015, India
| | - Rohit R Bhosale
- Department of Pharmaceutics, Krishna Foundation's Jaywant Institute of Pharmacy, Wathar, Tal. Karad, Maharashtra, 415539, India
| | - Nazima Haider
- Department of Pathology, College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia
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4
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Rahdan F, Abedi F, Dianat-Moghadam H, Sani MZ, Taghizadeh M, Alizadeh E. Autophagy-based therapy for hepatocellular carcinoma: from standard treatments to combination therapy, oncolytic virotherapy, and targeted nanomedicines. Clin Exp Med 2024; 25:13. [PMID: 39621122 PMCID: PMC11611955 DOI: 10.1007/s10238-024-01527-5] [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: 10/09/2024] [Accepted: 11/22/2024] [Indexed: 12/06/2024]
Abstract
Human hepatocellular carcinoma (HCC) has been identified as a significant cause of mortality worldwide. In recent years, extensive research has been conducted to understand the underlying mechanisms of autophagy in the pathogenesis of the disease, with the aim of developing novel therapeutic agents. Targeting autophagy with conventional therapies in invasive HCC has opened up new opportunities for treatment. However, the emergence of resistance and the immunosuppressive tumor environment highlight the need for combination therapy or specific targeting, as well as an efficient drug delivery system to ensure targeted tumor areas receive sufficient doses without affecting normal cells or tissues. In this review, we discuss the findings of several studies that have explored autophagy as a potential therapeutic approach in HCC. We also outline the potential and limitations of standard therapies for autophagy modulation in HCC treatment. Additionally, we discuss how different combination therapies, nano-targeted strategies, and oncolytic virotherapy could enhance autophagy-based HCC treatment in future research.
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Affiliation(s)
- Fereshteh Rahdan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Abedi
- Clinical Research Development, Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Dianat-Moghadam
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 8174673461, Iran.
- Pediatric Inherited Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, 8174673461, Iran.
| | - Maryam Zamani Sani
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Taghizadeh
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Effat Alizadeh
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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5
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Chen L, He Y, Lan J, Li Z, Gu D, Nie W, Zhang T, Ding Y. Advancements in nano drug delivery system for liver cancer therapy based on mitochondria-targeting. Biomed Pharmacother 2024; 180:117520. [PMID: 39395257 DOI: 10.1016/j.biopha.2024.117520] [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: 07/10/2024] [Revised: 09/26/2024] [Accepted: 10/04/2024] [Indexed: 10/14/2024] Open
Abstract
Based on poor efficacy and non-specific toxic side effects of conventional drug therapy for liver cancer, nano-based drug delivery system (NDDS) offers the advantage of drug targeting delivery. Subcellular targeting of nanomedicines on this basis enables more precise and effective termination of tumor cells. Mitochondria, as the crucial cell powerhouse, possesses distinctive physical and chemical properties in hepatoma cells different from that in hepatic cells, and controls apoptosis, tumor metastasis, and cellular drug resistance in hepatoma cells through metabolism and dynamics, which serves as a good choice for drug targeting delivery. Thus, mitochondria-targeting NDDS have become a recent research focus, showcasing the design of cationic nanoparticles, metal nanoparticles, mitochondrial peptide modification and so on. Although many studies have shown good results regarding anti-tumor efficacy, it is a long way to go before the successful translation of clinical application. Based on these, we summarized the specificity and importance of mitochondria in hepatoma cells, and reviewed the current mitochondria-targeting NDDS for liver cancer therapy, aiming to provide a better understanding for current development process, strengths and weaknesses of mitochondria-targeting NDDS as well as informing subsequent improvements and developments.
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Affiliation(s)
- Lixia Chen
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yitian He
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Jinshuai Lan
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zhe Li
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Donghao Gu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wenlong Nie
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Tong Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Yue Ding
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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6
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Li Y, Wang J, Li Y, Luo Z, Peng T, Zou T. Nanomaterials based on hollow gold nanospheres for cancer therapy. Regen Biomater 2024; 11:rbae126. [PMID: 39664940 PMCID: PMC11631698 DOI: 10.1093/rb/rbae126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 09/30/2024] [Accepted: 10/10/2024] [Indexed: 12/13/2024] Open
Abstract
Gold nanoparticles have recently been exploited as versatile nanocarriers in diagnostic and therapeutic drug delivery for cancer nanomedicine, owing to their biocompatibility, low biotoxicity, surface modifiability and plasma optical properties. A variety of gold nanoparticles have emerged for drug delivery, mainly including gold nanorods, gold nanocages, gold nanostars, gold solid nanospheres and hollow gold nanospheres (HGNs). Among these, HGNs have widely been studied for their higher photothermal conversion efficiency, wider spectral absorption range and stronger surface-enhanced Raman scattering compared with solid gold nanospheres. Therefore, nowadays, researchers prefer to use HGNs to other metal nanocarriers, which can not only play the role of controlled-release drugs but also act as photothermal agents for tumor therapy and diagnosis, due to their properties of surface modification. Combined with the Au-S bond on the surface of HGNs, the targeted preparation is loaded to achieve precise drug delivery. With the assistance of the photothermal characteristics of HGNs themselves, the efficacy of loaded drugs in HGNs is enhanced. In addition, HGNs also have vital values in the field of bioimaging, which serve as photothermal imaging agents and Raman scattering-guided preparations due to their surface-enhanced Raman scattering properties to assist researchers in achieving the purpose of tumor diagnosis. In this review, we summarize the synthesis methods of HGNs and the recent application of HGNs-based nanomaterials in the field of cancer diagnosis and therapy. In addition, the issues to be addressed were pointed out for a bright prospect of HGNs-based nanomaterials.
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Affiliation(s)
- You Li
- State Key Laboratory of Refractories and Metallurgy, Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P.R. China
| | - Jing Wang
- Laboratory for Genetic Engineering of Antibodies and Functional Proteins, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China
| | - Ying Li
- State Key Laboratory of Refractories and Metallurgy, Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P.R. China
| | - Ziqiang Luo
- State Key Laboratory of Refractories and Metallurgy, Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P.R. China
| | - Tao Peng
- GEM (Wuhan) Urban Mining Industrial Group Co., Ltd, Wuhan 430415, P.R. China
| | - Tao Zou
- State Key Laboratory of Refractories and Metallurgy, Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P.R. China
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7
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Li Y, Gao X, Li Y, Yan S, Zhang Y, Zheng X, Gu Q. Endocytosis: the match point of nanoparticle-based cancer therapy. J Mater Chem B 2024; 12:9435-9458. [PMID: 39192831 DOI: 10.1039/d4tb01227e] [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: 08/29/2024]
Abstract
Nanomedicine has inspired a ground-breaking strategy for cancer therapy. By intelligently assembling diverse moieties to form nanoparticles, numerous functionalities such as controlled release, synergistic efficiency, and in situ killing can be achieved. The emerging nanoparticles have been designed with elevated targeting efficiency as targeting cancer cells is the primary requirement for nanoparticles. However, effective targeting does not guarantee therapeutic effects as endocytosis is a prerequisite for nanoparticles to exert effects. The recent decade has witnessed the rapid development of endocytosis-oriented nanoparticles, and this review subtly analyzes, categorizes, and exemplifies these nanoparticles according to their biological internalization patterns, and the correlation between the endocytosis mechanism and the property of nanoparticles is bridged. Based on the interdisciplinary vision, the present challenges and future perspectives of nanoparticle design for successful endocytosis are discussed, highlighting the potential strategies for the future development of endocytosis-oriented nanoparticles, thus facilitating the endocytosis-oriented strategy from bench to bedside. The undeniable fact is that endocytosis-oriented nanoparticles will definitely bring new blood to the next generation of advanced cancer therapies.
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Affiliation(s)
- Yonglu Li
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
| | - Xin Gao
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
| | - Yapeng Li
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
| | - Shihai Yan
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
| | - Yiru Zhang
- Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-food Processing, Fuli Institute of Food Science, National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang University, Hangzhou 310058, People's Republic of China
| | - Xiaodong Zheng
- Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-food Processing, Fuli Institute of Food Science, National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang University, Hangzhou 310058, People's Republic of China
| | - Qing Gu
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
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8
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Wang Y, Li N, Qu L, Zhang M, Li Z, Li X, Cai D. Hemoglobin nanoclusters-mediated regulation of KPNA4 in hypoxic tumor microenvironment enhances photodynamic therapy in hepatocellular carcinoma. J Nanobiotechnology 2024; 22:473. [PMID: 39135024 PMCID: PMC11318167 DOI: 10.1186/s12951-024-02717-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 07/09/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a highly malignant tumor known for its hypoxic environment, which contributes to resistance against the anticancer drug Sorafenib (SF). Addressing SF resistance in HCC requires innovative strategies to improve tumor oxygenation and effectively deliver therapeutics. RESULTS In our study, we explored the role of KPNA4 in mediating hypoxia-induced SF resistance in HCC. We developed hemoglobin nanoclusters (Hb-NCs) capable of carrying oxygen, loaded with indocyanine green (ICG) and SF, named HPRG@SF. In vitro, HPRG@SF targeted HCC cells, alleviated hypoxia, suppressed KPNA4 expression, and enhanced the cytotoxicity of PDT against hypoxic, SF-resistant HCC cells. In vivo experiments supported these findings, showing that HPRG@SF effectively improved the oxygenation within the tumor microenvironment and countered SF resistance through combined photodynamic therapy (PDT). CONCLUSION The combination of Hb-NCs with ICG and SF, forming HPRG@SF, presents a potent strategy to overcome drug resistance in hepatocellular carcinoma by improving hypoxia and employing PDT. This approach not only targets the hypoxic conditions that underlie resistance but also provides a synergistic anticancer effect, highlighting its potential for clinical applications in treating resistant HCC.
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Affiliation(s)
- Yiliang Wang
- Department of Anesthesiology, The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China
| | - Nu Li
- Department of breast surgery, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China
| | - Letian Qu
- Department of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China
| | - Mu Zhang
- Department of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China
| | - Zhuo Li
- The Fourth People's Hospital of Shenyang, 110002, Liaoning Province, China
| | - Xiang Li
- Department of Neurosurgery, The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
| | - Dasheng Cai
- Department of Anesthesiology, The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
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Ye J, Wu Q, Ji Q, You S, Gao S, Zhao G, Xu Q, Liu K, Li P. Au/Doc/Quer@PDA/A10-3.2 Nanoparticles for targeted treatment of docetaxel-resistant prostate cancer. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2024; 35:1631-1655. [PMID: 38769597 DOI: 10.1080/09205063.2024.2346395] [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: 11/30/2023] [Accepted: 04/04/2024] [Indexed: 05/22/2024]
Abstract
Docetaxel (Doc), as a first-line chemotherapy drug for prostate cancer (PC), often loses its therapeutic efficacy due to acquired resistance and lack of targeting specificity. Therefore, there is a need to develop a novel drug that can overcome Doc resistance and enhance its targeting ability to inhibit PC progression. In this study, we prepared Au/Doc/Quer@PDA/A10-3.2 nanoparticles (NPs) composite drug by encapsulating Doc and quercetin (Quer) within polydopamine (PDA)-coated Au NPs and further modifying them with RNA oligonucleotide aptamer A10-3.2. A10-3.2 was used for specific targeting of prostate-specific membrane antigen (PSMA)-positive PC cells (LNCaP). Quer was employed to reverse the resistance of Doc-resistant cell line (LNCaP/R) to Doc. Physical characterization using ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR) confirmed the successful preparation of Au/Doc/Quer@PDA/A10-3.2 NPs. Fluorescence imaging and flow cytometry experiments demonstrated the targeting ability of Au/Doc/Quer@PDA/A10-3.2 NPs towards PSMA-positive LNCaP/R cells. Cell proliferation, apoptosis, invasion, and migration experiments revealed that Quer reversed the resistance of LNCaP/R cells to Doc. Immunoblotting experiments further confirmed the mechanism behind sensitization of chemotherapy by Quer. Finally, we evaluated the therapeutic efficacy of Au/Doc/Quer@PDA/A10-3.2 NPs in a mouse model of PC. In conclusion, this study synthesized and validated a novel nano-composite drug (Au/Doc/Quer@PDA/A10-3.2 NPs) for combating Doc-resistant PC, which could potentially be applied in clinical treatment of PC.
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Affiliation(s)
- Junjie Ye
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
| | - Qi Wu
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
| | - Qingfen Ji
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
| | - Shengjie You
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
| | - Song Gao
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
| | - Guanan Zhao
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
| | - Qiangqiang Xu
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
| | - Ken Liu
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
| | - Peng Li
- Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China
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10
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Fan QQ, Tian H, Cheng JX, Zou JB, Luan F, Qiao JX, Zhang D, Tian Y, Zhai BT, Guo DY. Research progress of sorafenib drug delivery system in the treatment of hepatocellular carcinoma: An update. Biomed Pharmacother 2024; 177:117118. [PMID: 39002440 DOI: 10.1016/j.biopha.2024.117118] [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: 04/09/2024] [Revised: 07/01/2024] [Accepted: 07/08/2024] [Indexed: 07/15/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in the contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes the onset and progression of the disease. Moreover, advanced HCC is insensitive to chemotherapy, making traditional clinical treatment unable to block cancer development. Sorafenib (SFB) is a first-line targeted drug for advanced HCC patients with anti-angiogenesis and anti-tumor cell proliferation effects. However, the efficacy of SFB is constrained by its off-target distribution, rapid metabolism, and multi-drug resistance. In recent years, nanoparticles based on a variety of materials have been demonstrated to enhance the targeting and therapeutic efficacy of SFB against HCC. Concurrently, the advent of joint drug delivery systems has furnished crucial empirical evidence for reversing SFB resistance. This review will summarize the application of nanotechnology in the field of HCC treatment over the past five years. It will focus on the research progress of SFB delivery systems combined with multiple therapeutic modalities in HCC treatment.
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Affiliation(s)
- Qiang-Qiang Fan
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Huan Tian
- Xi'an Hospital of Traditional Chinese Medicine, 710021, China
| | - Jiang-Xue Cheng
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Jun-Bo Zou
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Fei Luan
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Jia-Xin Qiao
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Dan Zhang
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Yuan Tian
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Bing-Tao Zhai
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China.
| | - Dong-Yan Guo
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China.
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11
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Guo Y, Li B, Xie H, Wu C, Wang G, Yao K, Li L. The therapeutic efficacy of different configuration nano-polydopamine drug carrier systems with photothermal synergy against head and neck squamous cell carcinoma. Regen Biomater 2024; 11:rbae073. [PMID: 39027362 PMCID: PMC11256922 DOI: 10.1093/rb/rbae073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 06/02/2024] [Accepted: 06/05/2024] [Indexed: 07/20/2024] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor worldwide. Considering its special anatomical site and the progressive resistance to chemotherapy drugs, the development of more effective, minimally invasive and precise treatment methods is urgently needed. Nanomaterials, given their special properties, can be used as drug carrier systems to improve the therapeutic effect and reduce the adverse effects. The drug carrier systems with photothermal effect can promote the killing of cancer cells and help overcome drug resistance through heat stress. We selected dopamine, a simple raw material, and designed and synthesized three different configurations of nano-polydopamine (nPDA) nanomaterials, including nPDA balls, nPDA plates and porous nPDA balls. In addition to the self-polymerization and self-assembly, nPDA has high photothermal conversion efficiency and can be easily modified. Moreover, we loaded cisplatin into three different configurations of nPDA, creating nPDA-cis (the nano-drug carrier system with cisplatin), and comparatively studied the properties and antitumor effects of all the nPDA and nPDA-cis materials in vitro and nPDA-cis in vivo. We found that the photothermal effect of the nPDA-cis balls drug carrier system had synergistic effect with cisplatin, resulting in excellent antitumor effect and good clinical application prospects. The comparison of the three different configurations of drug carrier systems suggested the importance of optimizing the spatial configuration design and examining the physical and chemical properties in the future development of nano-drug carrier systems. In this study, we also noted the duality and complexity of the influences of heat stress on tumors in vitro and in vivo. The specific mechanisms and the synergy with chemotherapy and immunotherapy will be an important research direction in the future.
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Affiliation(s)
- Yuhao Guo
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
- Department of Stomatology, Xinqiao Hospital of Army Medical University, Chongqing 400037,China
| | - Bo Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
| | - Huixu Xie
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
- Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
| | - Chenzhou Wu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
- Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
| | - Guixue Wang
- State and Local Joint Engineering Laboratory, Bioengineering College of Chongqing University, Chongqing 400044,China
| | - Kexin Yao
- Multi-Scale Porous Materials Center, Institute of Advanced Interdisciplinary Studies, School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044,China
| | - Longjiang Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
- Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041,China
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12
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Huang J, Guo L, Huang X, Yu X, Lin L, Jiang X, Bai Z, Li Z. Multimodal Imaging-Guided Synergistic Photodynamic Therapy Using Carbonized Zn/Co Metal-Organic Framework Loaded with Cytotoxin Against Liver Cancer. Int J Nanomedicine 2024; 19:4163-4180. [PMID: 38751660 PMCID: PMC11095517 DOI: 10.2147/ijn.s453275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 04/23/2024] [Indexed: 05/18/2024] Open
Abstract
Purpose The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2). Methods Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD's active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells. Results Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity. Conclusion The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.
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Affiliation(s)
- Jingmei Huang
- Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China
| | - Lianshan Guo
- Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China
| | - Xiaoxiao Huang
- Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China
| | - Xiaoping Yu
- Department of Radiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China
| | - Liqiao Lin
- Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China
| | - Xinlin Jiang
- Department of General Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China
| | - Zhihao Bai
- College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China
| | - Zhengzhao Li
- Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China
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13
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Zhou XQ, Li YP, Dang SS. Precision targeting in hepatocellular carcinoma: Exploring ligand-receptor mediated nanotherapy. World J Hepatol 2024; 16:164-176. [PMID: 38495282 PMCID: PMC10941735 DOI: 10.4254/wjh.v16.i2.164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/10/2024] [Accepted: 01/18/2024] [Indexed: 02/27/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality. Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages, but it is often ineffective and suffers from problems such as multidrug resistance, rapid drug clearance, nonspecific targeting, high side effects, and low drug accumulation in tumor cells. In response to these limitations, recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC. This review focuses on recent advances in nanoparticle-based targeted drug delivery systems, with special attention to various receptors overexpressed on HCC cells. These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC. We comprehensively summarize the current understanding of these receptors, their role in nanoparticle targeting, and the impact of such targeted therapies on HCC. By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies, more effective and precise treatment of HCC can be achieved.
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Affiliation(s)
- Xia-Qing Zhou
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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14
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Xiang Z, Zhang J, Zhou C, Zhang B, Chen N, Li M, Fu D, Wang Y. Near-Infrared Remotely Controllable Shape Memory Biodegradable Occluder Based on Poly(l-lactide- co-ε-caprolactone)/Gold Nanorod Composite. ACS APPLIED MATERIALS & INTERFACES 2023; 15:42341-42353. [PMID: 37647023 DOI: 10.1021/acsami.3c09852] [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: 09/01/2023]
Abstract
Biodegradable occluders, which can efficiently eliminate the complications caused by permanent foreign implants, are considered to be the next-generation devices for the interventional treatment of congenital heart disease. However, the controllability of the deployment process of degradable occluders remains a challenge. In this work, a near-infrared (NIR) remotely controllable biodegradable occluder is explored by integrating poly(l-lactide-co-ε-caprolactone) (PLCL) with poly(ethylene glycol)-modified gold nanorods (GNR/PEG). The caprolactone structural units can effectively increase the toughness of poly(l-lactide) and reduce the shape-memory transition temperature of the occluder to a more tissue-friendly temperature. Gold nanorods endow the PLCL-GNR/PEG composite with an excellent photothermal effect. The obtained occluder can be easily loaded into a catheter for transport and spatiotemporally expanded under irradiation with near-infrared light to block the defect site. Both in vitro and in vivo biological experiments showed that PLCL-GNR/PEG composites have good biocompatibility, and the PEGylated gold nanorods could improve the hemocompatibility of the composites to a certain extent by enhancing their hydrophilicity. As a thermoplastic shape-memory polymer, PLCL-GNR/PEG can be easily processed into various forms and structures for different patients and lesions. Therefore, PLCL-GNR/PEG has the potential to be considered as a competitive biodegradable material not only for occluders but also for other biodegradable implants.
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Affiliation(s)
- Zhen Xiang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Jiayi Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Chen Zhou
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Bo Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Nuoya Chen
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Mingyu Li
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Daihua Fu
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Yunbing Wang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
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15
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Ibarra J, Encinas-Basurto D, Almada M, Juárez J, Valdez MA, Barbosa S, Taboada P. Gold Half-Shell-Coated Paclitaxel-Loaded PLGA Nanoparticles for the Targeted Chemo-Photothermal Treatment of Cancer. MICROMACHINES 2023; 14:1390. [PMID: 37512701 PMCID: PMC10384528 DOI: 10.3390/mi14071390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/16/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023]
Abstract
Conventional cancer therapies suffer from nonspecificity, drug resistance, and a poor bioavailability, which trigger severe side effects. To overcome these disadvantages, in this study, we designed and evaluated the in vitro potential of paclitaxel-loaded, PLGA-gold, half-shell nanoparticles (PTX-PLGA/Au-HS NPs) conjugated with cyclo(Arg-Gly-Asp-Phe-Lys) (cyRGDfk) as a targeted chemo-photothermal therapy system in HeLa and MDA-MB-231 cancer cells. A TEM analysis confirmed the successful gold half-shell structure formation. High-performance liquid chromatography showed an encapsulation efficiency of the paclitaxel inside nanoparticles of more than 90%. In the release study, an initial burst release of about 20% in the first 24 h was observed, followed by a sustained drug release for a period as long as 10 days, reaching values of about 92% and 49% for NPs with and without near infrared laser irradiation. In in vitro cell internalization studies, targeted nanoparticles showed a higher accumulation than nontargeted nanoparticles, possibly through a specific interaction of the cyRGDfk with their homologous receptors, the ανβ3 y ανβ5 integrins on the cell surface. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, reducing the cell viability to 23% for the HeLa cells and 31% for the MDA-MB-231 cells. Thus, our results indicate that these multifuncional nanoparticles can be considered to be a promising targeted chemo-photothermal therapy system against cancer.
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Affiliation(s)
- Jaime Ibarra
- Departamento de Física, Matemáticas e Ingeniería, Universidad de Sonora, Campus Navojoa, Navojoa 85880, Sonora, Mexico
| | - David Encinas-Basurto
- Departamento de Física, Matemáticas e Ingeniería, Universidad de Sonora, Campus Navojoa, Navojoa 85880, Sonora, Mexico
| | - Mario Almada
- Departamento de Ciencias Químico-Biológicas y Agropecuarias, Universidad de Sonora, Campus Navojoa, Navojoa 85880, Sonora, Mexico
| | - Josué Juárez
- Departamento de Física, Universidad de Sonora, Campus Hermosillo, Hermosillo 83000, Sonora, Mexico
| | - Miguel Angel Valdez
- Departamento de Física, Universidad de Sonora, Campus Hermosillo, Hermosillo 83000, Sonora, Mexico
| | - Silvia Barbosa
- Departamento de Física de Partículas, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, A Coruña, Spain
| | - Pablo Taboada
- Departamento de Física de Partículas, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, A Coruña, Spain
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16
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Yu C, Jiang W, Li B, Hu Y, Liu D. The Role of Integrins for Mediating Nanodrugs to Improve Performance in Tumor Diagnosis and Treatment. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:nano13111721. [PMID: 37299624 DOI: 10.3390/nano13111721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 05/18/2023] [Accepted: 05/23/2023] [Indexed: 06/12/2023]
Abstract
Integrins are heterodimeric transmembrane proteins that mediate adhesive connections between cells and their surroundings, including surrounding cells and the extracellular matrix (ECM). They modulate tissue mechanics and regulate intracellular signaling, including cell generation, survival, proliferation, and differentiation, and the up-regulation of integrins in tumor cells has been confirmed to be associated with tumor development, invasion, angiogenesis, metastasis, and therapeutic resistance. Thus, integrins are expected to be an effective target to improve the efficacy of tumor therapy. A variety of integrin-targeting nanodrugs have been developed to improve the distribution and penetration of drugs in tumors, thereby, improving the efficiency of clinical tumor diagnosis and treatment. Herein, we focus on these innovative drug delivery systems and reveal the improved efficacy of integrin-targeting methods in tumor therapy, hoping to provide prospective guidance for the diagnosis and treatment of integrin-targeting tumors.
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Affiliation(s)
- Chi Yu
- College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China
| | - Wei Jiang
- Institute of Materials Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210093, China
| | - Bin Li
- Department of Biochemistry and Molecular Biology, Medical College, Guangxi University of Science and Technology, Liuzhou 545005, China
| | - Yong Hu
- Institute of Materials Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210093, China
| | - Dan Liu
- College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China
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Yi J, Luo X, Xing J, Gedanken A, Lin X, Zhang C, Qiao G. Micelle encapsulation zinc-doped copper oxide nanocomposites reverse Olaparib resistance in ovarian cancer by disrupting homologous recombination repair. Bioeng Transl Med 2023; 8:e10507. [PMID: 37206208 PMCID: PMC10189445 DOI: 10.1002/btm2.10507] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 01/22/2023] [Accepted: 03/04/2023] [Indexed: 03/31/2024] Open
Abstract
Micelle Encapsulation Zinc-doped copper oxide nanocomposites (MEnZn-CuO NPs) is a novel doped metal nanomaterial prepared by our group based on Zinc doped copper oxide nanocomposites (Zn-CuO NPs) using non-micellar beam. Compared with Zn-CuO NPs, MEnZn-CuO NPs have uniform nanoproperties and high stability. In this study, we explored the anticancer effects of MEnZn-CuO NPs on human ovarian cancer cells. In addition to affecting cell proliferation, migration, apoptosis and autophagy, MEnZn-CuO NPs have a greater potential for clinical application by inducing HR repair defects in ovarian cancer cells in combination with poly (ADP-ribose) polymerase inhibitors for lethal effects.
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Affiliation(s)
- Jingyan Yi
- Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular ResearchSouthwest Medical UniversityLuzhouSichuan646000China
| | - Xin Luo
- Department of Pharmacology, School of Pharmacy, Nucleic Acid Medicine of Luzhou Key LaboratorySouthwest Medical UniversityLuzhouSichuan646000China
| | - Jinshan Xing
- Department of NeurosurgeryThe Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhouSichuan646000China
| | - Aharon Gedanken
- Center for Advanced Materials and NanotechnologyBar‐Ilan UniversityRamat Gan52900Israel
| | - Xiukun Lin
- College of Marine SciencesBeibu Gulf University12 Binhai RoadQinzhou535011GuangxiChina
| | - Chunxiang Zhang
- Nucleic Acid Medicine of Luzhou Key Laboratory, Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular ResearchSouthwest Medical UniversityLuzhouSichuan646000China
| | - Gan Qiao
- Department of Pharmacology, School of Pharmacy, Nucleic Acid Medicine of Luzhou Key LaboratorySouthwest Medical UniversityLuzhouSichuan646000China
- School of Pharmacy, Central Nervous System Drug Key Laboratory of Sichuan Province, Nucleic Acid Medicine of Luzhou Key Laboratory, Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular ResearchSouthwest Medical UniversityLuzhou646000SichuanChina
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18
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Yu H, Wang Y, Chen Y, Cui M, Yang F, Wang P, Ji M. Transmissible H-aggregated NIR-II fluorophore to the tumor cell membrane for enhanced PTT and synergistic therapy of cancer. NANO CONVERGENCE 2023; 10:3. [PMID: 36609947 PMCID: PMC9823176 DOI: 10.1186/s40580-022-00352-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 12/15/2022] [Indexed: 06/17/2023]
Abstract
Photothermal therapy (PTT) combined with second near-infrared (NIR-II) fluorescence imaging (FI) has received increasing attention owing to its capacity for precise diagnosis and real-time monitoring of the therapeutic effects. It is of great clinical value to study organic small molecular fluorophores with both PTT and NIR-II FI functions. In this work, we report a skillfully fluorescent lipid nanosystem, the RR9 (RGDRRRRRRRRRC) peptide-coated anionic liposome loaded with organic NIR-II fluorophore IR-1061 and chemotherapeutic drug carboplatin, which is named RRIALP-C4. According to the structural interaction between IR-1061 and phospholipid bilayer demonstrated by molecular dynamics simulations, IR-1061 is rationally designed to possess the H-aggregated state versus the free state, thus rendering RRIALP-C4 with the activated dual-channel integrated function of intravital NIR-II FI and NIR-I PTT. Functionalization of RRIALP-C4 with RR9 peptide endows the specifically targeting capacity for αvβ3-overexpressed tumor cells and, more importantly, allows IR-1061 to transfer the H-aggregated state from liposomes to the tumor cell membrane through enhanced membrane fusion, thereby maintaining its PTT effect in tumor tissues. In vivo experiments demonstrate that RRIALP-C4 can effectively visualize tumor tissues and systemic blood vessels with a high sign-to-background ratio (SBR) to realize the synergistic treatment of thermochemotherapy by PTT synergistically with temperature-sensitive drug release. Therefore, the strategy of enhanced PTT through H-aggregation of NIR-II fluorophore in the tumor cell membrane has great potential for developing lipid nanosystems with integrated diagnosis and treatment function.
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Affiliation(s)
- Haoli Yu
- State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Yuesong Wang
- State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Yan Chen
- State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Mengyuan Cui
- State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Fang Yang
- State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
| | - Peng Wang
- Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, 210009, China.
| | - Min Ji
- State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
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Cao D, Ding J. Recent advances in regenerative biomaterials. Regen Biomater 2022; 9:rbac098. [PMID: 36518879 PMCID: PMC9745784 DOI: 10.1093/rb/rbac098] [Citation(s) in RCA: 106] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/23/2022] [Accepted: 12/01/2022] [Indexed: 07/22/2023] Open
Abstract
Nowadays, biomaterials have evolved from the inert supports or functional substitutes to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of 'biomaterials', and a typical new insight is the concept of tissue induction biomaterials. The term 'regenerative biomaterials' and thus the contents of this article are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers and bio-derived materials. As the application aspects are concerned, this article introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, 3D bioprinting, wound healing and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of coronavirus disease 2019, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (i) creation of new materials is the source of innovation; (ii) modification of existing materials is an effective strategy for performance improvement; (iii) biomaterial degradation and tissue regeneration are required to be harmonious with each other; (iv) host responses can significantly influence the clinical outcomes; (v) the long-term outcomes should be paid more attention to; (vi) the noninvasive approaches for monitoring in vivo dynamic evolution are required to be developed; (vii) public health emergencies call for more research and development of biomaterials; and (viii) clinical translation needs to be pushed forward in a full-chain way. In the future, more new insights are expected to be shed into the brilliant field-regenerative biomaterials.
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Affiliation(s)
- Dinglingge Cao
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Jiandong Ding
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
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20
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Egorova EA, Nikitin MP. Delivery of Theranostic Nanoparticles to Various Cancers by Means of Integrin-Binding Peptides. Int J Mol Sci 2022; 23:ijms232213735. [PMID: 36430214 PMCID: PMC9696485 DOI: 10.3390/ijms232213735] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 10/27/2022] [Accepted: 11/02/2022] [Indexed: 11/11/2022] Open
Abstract
Active targeting of tumors is believed to be the key to efficient cancer therapy and accurate, early-stage diagnostics. Active targeting implies minimized off-targeting and associated cytotoxicity towards healthy tissue. One way to acquire active targeting is to employ conjugates of therapeutic agents with ligands known to bind receptors overexpressed onto cancer cells. The integrin receptor family has been studied as a target for cancer treatment for almost fifty years. However, systematic knowledge on their effects on cancer cells, is yet lacking, especially when utilized as an active targeting ligand for particulate formulations. Decoration with various integrin-targeting peptides has been reported to increase nanoparticle accumulation in tumors ≥ 3-fold when compared to passively targeted delivery. In recent years, many newly discovered or rationally designed integrin-binding peptides with excellent specificity towards a single integrin receptor have emerged. Here, we show a comprehensive analysis of previously unreviewed integrin-binding peptides, provide diverse modification routes for nanoparticle conjugation, and showcase the most notable examples of their use for tumor and metastases visualization and eradication to date, as well as possibilities for combined cancer therapies for a synergetic effect. This review aims to highlight the latest advancements in integrin-binding peptide development and is directed to aid transition to the development of novel nanoparticle-based theranostic agents for cancer therapy.
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Affiliation(s)
- Elena A. Egorova
- Department of Nanobiomedicine, Sirius University of Science and Technology, 1 Olympic Ave., 354340 Sirius, Russia
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 1 Meditsinskaya Str., 603081 Nizhny Novgorod, Russia
| | - Maxim P. Nikitin
- Department of Nanobiomedicine, Sirius University of Science and Technology, 1 Olympic Ave., 354340 Sirius, Russia
- Moscow Institute of Physics and Technology, 9 Institutskiy per., 141701 Dolgoprudny, Russia
- Correspondence:
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Meng Z, Wang B, Liu Y, Wan Y, Liu Q, Xu H, Liang R, Shi Y, Tu P, Wu H, Xu C. Mitochondria-targeting Polydopamine-coated Nanodrugs for Effective Photothermal- and Chemo- Synergistic therapies Against Lung Cancer. Regen Biomater 2022; 9:rbac051. [PMID: 35958515 PMCID: PMC9362997 DOI: 10.1093/rb/rbac051] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 06/27/2022] [Accepted: 07/05/2022] [Indexed: 11/26/2022] Open
Abstract
Targeting mitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance. Here, a mitochondria-targeting nanoparticle (TOS-PDA-PEG-TPP) was designed to precisely deliver polydopamine (PDA) as the photothermal agent and alpha-tocopherol succinate (α-TOS) as the chemotherapeutic drug to the mitochondria of the tumor cells, which inhibits the tumor growth through chemo- and photothermal- synergistic therapies. TOS-PDA-PEG-TPP was constructed by coating PDA on the surface of TOS NPs self-assembled by α-TOS, followed by grafting PEG and triphenylphosphonium (TPP) on their surface to prolong the blood circulation time and target delivery of TOS and PDA to the mitochondria of tumor cells. In vitro studies showed that TOS-PDA-PEG-TPP could be efficiently internalized by tumor cells and accumulated at mitochondria, resulting in cellular apoptosis and synergistic inhibition of tumor cell proliferation. In vivo studies demonstrated that TOS-PDA-PEG-TPP could be efficiently localized at tumor sites and significantly restrain the tumor growth under NIR irradiation without apparent toxicity or deleterious effects. Conclusively, the combination strategy adopted for functional nanodrugs construction aimed at target-delivering therapeutic agents with different action mechanisms to the same intracellular organelles can be extended to other nanodrugs-dependent therapeutic systems.
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Affiliation(s)
- Ziyu Meng
- College of Science, Gansu Agricultural University, Lanzhou 730070, China
- Integrative Cancer Center & Cancer Clinical Research Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610047, China
| | - Binchao Wang
- College of Science, Gansu Agricultural University, Lanzhou 730070, China
| | - Yiqiang Liu
- Integrative Cancer Center & Cancer Clinical Research Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610047, China
| | - Yejian Wan
- Integrative Cancer Center & Cancer Clinical Research Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610047, China
| | - Qianshi Liu
- Integrative Cancer Center & Cancer Clinical Research Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610047, China
| | - Huasheng Xu
- Integrative Cancer Center & Cancer Clinical Research Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610047, China
| | - Renchuan Liang
- Integrative Cancer Center & Cancer Clinical Research Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610047, China
| | - Ying Shi
- Integrative Cancer Center & Cancer Clinical Research Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610047, China
| | - Peng Tu
- Correspondence address: Tel: +86-28-85420852, E-mail: (P.T); (H.W); (C.X)
| | - Hong Wu
- Correspondence address: Tel: +86-28-85420852, E-mail: (P.T); (H.W); (C.X)
| | - Chuan Xu
- Correspondence address: Tel: +86-28-85420852, E-mail: (P.T); (H.W); (C.X)
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22
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Bergonzini C, Kroese K, Zweemer AJM, Danen EHJ. Targeting Integrins for Cancer Therapy - Disappointments and Opportunities. Front Cell Dev Biol 2022; 10:863850. [PMID: 35356286 PMCID: PMC8959606 DOI: 10.3389/fcell.2022.863850] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 02/16/2022] [Indexed: 12/29/2022] Open
Abstract
Integrins mediate adhesive interactions between cells and their environment, including neighboring cells and extracellular matrix (ECM). These heterodimeric transmembrane receptors bind extracellular ligands with their globular head domains and connect to the cytoskeleton through multi-protein interactions at their cytoplasmic tails. Integrin containing cell–matrix adhesions are dynamic force-responsive protein complexes that allow bidirectional mechanical coupling of cells with their environment. This allows cells to sense and modulate tissue mechanics and regulates intracellular signaling impacting on cell faith, survival, proliferation, and differentiation programs. Dysregulation of these functions has been extensively reported in cancer and associated with tumor growth, invasion, angiogenesis, metastasis, and therapy resistance. This central role in multiple hallmarks of cancer and their localization on the cell surface makes integrins attractive targets for cancer therapy. However, despite a wealth of highly encouraging preclinical data, targeting integrin adhesion complexes in clinical trials has thus far failed to meet expectations. Contributing factors to therapeutic failure are 1) variable integrin expression, 2) redundancy in integrin function, 3) distinct roles of integrins at various disease stages, and 4) sequestering of therapeutics by integrin-containing tumor-derived extracellular vesicles. Despite disappointing clinical results, new promising approaches are being investigated that highlight the potential of integrins as targets or prognostic biomarkers. Improvement of therapeutic delivery at the tumor site via integrin binding ligands is emerging as another successful approach that may enhance both efficacy and safety of conventional therapeutics. In this review we provide an overview of recent encouraging preclinical findings, we discuss the apparent disagreement between preclinical and clinical results, and we consider new opportunities to exploit the potential of integrin adhesion complexes as targets for cancer therapy.
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