1
|
Ali MS, Gupta G, Alsayari A, Wahab S, Kesharwani P. Biotinylated nanoparticles: A new frontier in nanomedicine and targeted cancer therapy. BIOMATERIALS ADVANCES 2025; 176:214366. [PMID: 40479769 DOI: 10.1016/j.bioadv.2025.214366] [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: 03/13/2025] [Revised: 05/11/2025] [Accepted: 05/31/2025] [Indexed: 06/16/2025]
Abstract
The development of targeted drug delivery systems has become a cornerstone of modern cancer therapy which provides a pathway to maximize treatment effectiveness while reducing side effects. Among the plethora of innovative strategies, biotinylated nanoparticles have evolved as a hopeful tool due to their ability to exploit the elevated expression of biotin receptors on cancerous cells. The design, synthesis, and functionalization of biotinylated nanoparticles for cancer treatment are thoroughly examined in this review article. By leveraging biotin's high affinity for biotin receptors, these nanoparticles achieve selective cancerous cell targeting, leading to enhanced drug bioavailability and cellular uptake. The discussion extends to the underlying mechanisms of drug release, receptor-mediated endocytosis, and strategies for achieving endosomal escape or pH-sensitive drug activation. Furthermore, the article also emphasizes how biotinylation in combination therapy allows for synergistic effects with immunomodulators, nucleic acids, and chemotherapeutic drugs. Preclinical studies are examined to underscore the translational potential of these systems. The review concludes by addressing current challenges, including scalability, and potential immunogenicity, while proposing future directions for optimizing biotinylated nanoparticles as a transformative approach in cancer treatment.
Collapse
Affiliation(s)
- Mohd Shoab Ali
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - Garima Gupta
- Graphic Era Hill University, Dehradun 248002, India; School of Allied Medical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Abdulrhman Alsayari
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia
| | - Shadma Wahab
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia
| | - Prashant Kesharwani
- Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, Madhya Pradesh 470003, India.
| |
Collapse
|
2
|
Liu X, Dhumal D, Santofimia-Castaño P, Liu J, Casanova M, Garcia-Muñoz AC, Perles-Barbacaru TA, Elkihel A, Zhang W, Roussel T, Galanakou C, Wu J, Zerva E, Dusetti N, Xia Y, Liang XJ, Viola A, Iovanna JL, Peng L. Self-assembling dendrimer nanodrug formulations for decreased hERG-related toxicity and enhanced therapeutic efficacy. SCIENCE ADVANCES 2025; 11:eadu9948. [PMID: 40561017 DOI: 10.1126/sciadv.adu9948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 05/20/2025] [Indexed: 06/28/2025]
Abstract
Cardiotoxicity, especially human ether-a-go-go-related gene (hERG)-related toxicity, is a leading cause of drug failure or market withdrawal. Reducing hERG binding to obviate potential cardiac toxicity is crucial. Nanotechnology has been applied to drug delivery for reducing drug toxicity and improving efficacy, but few studies have addressed hERG-related cardiotoxicity. We report the use of self-assembling dendrimer nanosystems for drug formulation and delivery, which effectively reduced hERG binding and associated toxicity while promoting therapeutic efficacy. Specifically, these dendrimer nanosystems efficiently encapsulated the antimalarial drug chloroquine, the anticancer agent doxorubicin, and the NUPR1 inhibitor ZZW115, all three having high affinity to hERG channels. These nanoformulations showed three- to eightfold reduced hERG binding affinity, which, in animal models, translated to abolished toxicity. These nanodrugs exhibited prolonged circulation, leading to enhanced accumulation at disease sites and improved treatment outcomes. This study highlights the potential of nanotechnology to reduce hERG binding and related toxicity while improving drug efficacy, offering valuable perspectives for drug development.
Collapse
Affiliation(s)
- Xi Liu
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
- Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS, UMR 7258, Institut Paoli-Calmettes, Aix Marseille Université, 13273 Marseille, France
| | - Dinesh Dhumal
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
| | - Patricia Santofimia-Castaño
- Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS, UMR 7258, Institut Paoli-Calmettes, Aix Marseille Université, 13273 Marseille, France
| | - Juan Liu
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China
| | - Marion Casanova
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
| | - Alicia Comino Garcia-Muñoz
- Aix Marseille University, CNRS, Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339, 13385 Marseille, France
| | - Teodora-Adriana Perles-Barbacaru
- Aix Marseille University, CNRS, Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339, 13385 Marseille, France
| | - Abdechakour Elkihel
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
| | - Wenzheng Zhang
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
- Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, No. 55 Daxuecheng South Road, Chongqing 401331, P. R. China
| | - Tom Roussel
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
| | - Christina Galanakou
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
| | - Jing Wu
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
- Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS, UMR 7258, Institut Paoli-Calmettes, Aix Marseille Université, 13273 Marseille, France
| | - Eleni Zerva
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
| | - Nelson Dusetti
- Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS, UMR 7258, Institut Paoli-Calmettes, Aix Marseille Université, 13273 Marseille, France
| | - Yi Xia
- Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, No. 55 Daxuecheng South Road, Chongqing 401331, P. R. China
| | - Xing-Jie Liang
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China
| | - Angèle Viola
- Aix Marseille University, CNRS, Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339, 13385 Marseille, France
| | - Juan L Iovanna
- Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS, UMR 7258, Institut Paoli-Calmettes, Aix Marseille Université, 13273 Marseille, France
| | - Ling Peng
- Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France
| |
Collapse
|
3
|
Chen Y, Qin Z, Wang Y, Gu B, Wang J, Zheng Y, Niu Y, Jia L. CD44-targeted virus-mimicking nanomedicine eliminates cancer stem cells and mitigates chemoresistance in head and neck squamous cell carcinoma. Mater Today Bio 2025; 32:101721. [PMID: 40242481 PMCID: PMC12002834 DOI: 10.1016/j.mtbio.2025.101721] [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: 01/16/2025] [Revised: 03/06/2025] [Accepted: 03/29/2025] [Indexed: 04/18/2025] Open
Abstract
Cancer stem cells (CSCs) play critical roles in tumor growth, metastasis, and chemoresistance. Although several small-molecule inhibitors designed to inhibit CSCs have been investigated in clinical trials, their inadequate tumor targeting and potential off-target side effects have led to poor outcomes. A CD44-targeted virus-mimicking nanomedicine encapsulating the BMI1 inhibitor PTC209 (PTC209@VNP-HA) was designed to treat head and neck squamous cell carcinoma (HNSCC). We used a dendritic mesoporous silica nanoparticle (MSN) as the core for virus-mimicking nanoparticle (VNP) formation after adding shell particles to the MSN surface. The VNP surface was then modified with hyaluronic acid (HA), and PTC209 was adsorbed by mesopores to form PTC209@VNP-HA. In this system, HA is used to target CD44+ CSCs. The rough surface of VNP-HA provided better drug delivery efficiency than smooth nanoparticles modified with HA. VNP-HA enhanced the cancer inhibitory effect of PTC209 12-fold compared to the administration of free PTC209, leading to significantly higher bioavailability of PTC209. Both in vitro and in vivo assays showed that PTC209@VNP-HA inhibited cancer stemness, proliferation, and metastasis in HNSCC. Mechanistically, this inhibitory effect is closely associated with DNA damage/apoptosis signaling. Using a series of preclinical models in murine systems, we confirmed that PTC209@VNP-HA eliminated BMI1+ CSCs, and greatly inhibited the proliferation and metastasis of HNSCC when combined with cisplatin. This study investigated PTC209@VNP-HA as a novel and potentially transformative HNSCC treatment option that eliminates CSCs, prevents metastasis, and overcomes cisplatin resistance.
Collapse
Affiliation(s)
- Yiwen Chen
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
- National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, PR China
| | - Zhen Qin
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
| | - Yujia Wang
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
| | - Baoxin Gu
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
| | - Jing Wang
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100091, PR China
| | - Yunfei Zheng
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
| | - Yuting Niu
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
| | - Lingfei Jia
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
- National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, PR China
- Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Institute of Advanced Clinical Medicine, Peking University, Beijing 100091, PR China
| |
Collapse
|
4
|
Shi Y, Li X, Li Z, Sun J, Gao T, Wei G, Guo Q. Nano-formulations in disease therapy: designs, advances, challenges, and future directions. J Nanobiotechnology 2025; 23:396. [PMID: 40448105 DOI: 10.1186/s12951-025-03442-7] [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: 03/03/2025] [Accepted: 05/05/2025] [Indexed: 06/02/2025] Open
Abstract
Nano-formulations, as an innovative drug delivery system, offer distinct advantages in enhancing drug administration methods, improving bioavailability, promoting biodegradability, and enabling targeted delivery. By exploiting the unique size advantages of nano-formulations, therapeutic agents, including drugs, genes, and proteins, can be precisely reorganized at the microscale level. This modification not only facilitates the precise release of these agents but also significantly enhances their efficacy while minimizing adverse effects, thereby creating novel opportunities for treatment of a wide range of diseases. In this review, we discuss recent advancements, challenges, and future perspectives in nano-formulations for therapeutic applications. For this aim, we firstly introduce the development, design, synthesis, and action mechanisms of nano-formulations. Then, we summarize their applications in disease diagnosis and treatment, especially in fields of oncology, pulmonology, cardiology, endocrinology, dermatology, and ophthalmology. Furthermore, we address the challenges associated with the medical applications of nanomaterials, and provide an outlook on future directions based on these considerations. This review offers a comprehensive examination of the current applications and potential significance of nano-formulations in disease diagnosis and treatment, thereby contributing to the advancement of modern medical therapies.
Collapse
Affiliation(s)
- YunYan Shi
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People's Republic of China
| | - Xiao Li
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People's Republic of China
| | - Zhiyuan Li
- Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People's Republic of China
| | - Jialin Sun
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People's Republic of China
| | - Tong Gao
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People's Republic of China
| | - Gang Wei
- College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, 266071, Shandong, People's Republic of China.
| | - Qie Guo
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People's Republic of China.
| |
Collapse
|
5
|
Venturini J, Chakraborty A, Baysal MA, Tsimberidou AM. Developments in nanotechnology approaches for the treatment of solid tumors. Exp Hematol Oncol 2025; 14:76. [PMID: 40390104 PMCID: PMC12090476 DOI: 10.1186/s40164-025-00656-1] [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: 04/04/2025] [Accepted: 04/16/2025] [Indexed: 05/21/2025] Open
Abstract
Nanotechnology has revolutionized cancer therapy by introducing advanced drug delivery systems that enhance therapeutic efficacy while reducing adverse effects. By leveraging various nanoparticle platforms-including liposomes, polymeric nanoparticles, and inorganic nanoparticles-researchers have improved drug solubility, stability, and bioavailability. Additionally, new nanodevices are being engineered to respond to specific physiological conditions like temperature and pH variations, enabling controlled drug release and optimizing therapeutic outcomes. Beyond drug delivery, nanotechnology plays a crucial role in the theranostic field due to the functionalization of specific materials that combine tumor detection and targeted treatment features. This review analyzes the clinical impact of nanotechnology, spanning from early-phase trials to pivotal phase 3 studies that have obtained regulatory approval, while also offering a critical perspective on the preclinical domain and its translational potential for future human applications. Despite significant progress, greater attention must be placed on key challenges, such as biocompatibility barriers and the lack of regulatory standardization, to ensure the successful translation of nanomedicine into routine clinical practice.
Collapse
Affiliation(s)
- Jacopo Venturini
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
- Current Affiliation: Department of Medical Oncology, Careggi University Hospital, Florence, Italy
| | - Abhijit Chakraborty
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Mehmet A Baysal
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Apostolia M Tsimberidou
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
| |
Collapse
|
6
|
Polara H, Shah T, Babanyinah G, Wang H, Bhadran A, Biewer MC, Stefan MC. Improved Drug Delivery through Amide-Functionalized Polycaprolactones: Enhanced Loading Capacity and Sustained Drug Release. Biomacromolecules 2025; 26:3213-3223. [PMID: 40304243 DOI: 10.1021/acs.biomac.5c00280] [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: 05/02/2025]
Abstract
Polymeric micelles are effective for drug delivery but often face instability, low drug loading capacity (DLC), and premature drug leakage. Herein, we report that disubstituted γ-amide functionalized ε-caprolactone (ε-CL) monomers double the substituent density per polymeric unit, enhancing micelle properties and improving drug delivery applications. Three hydrophobic ε-CL monomers with two propyl groups, two benzyl groups, and a combination of propyl and benzyl groups were synthesized. The obtained monomers were polymerized by ring-opening polymerization using poly(ethylene glycol) (PEG) as a macroinitiator and the hydrophilic block. The synthesized copolymers successfully self-assembled to form micelles, and doxorubicin (DOX) was loaded into all micelles. Poly(ethylene glycol)-b-poly(N-propyl-N-benzyl-7-oxopane-4-carboxamide) (PEG-b-PBnPyCL) exhibited 7.33 wt % DLC with pH-responsive drug release in acidic conditions. In addition, the DOX-loaded micelles of PEG-b-PBnPyCL exhibited nearly 20% cell viability in MDA-MB-231 cancer cells. These results contribute to advancing polymeric micelles as drug carriers with clinical translation potential.
Collapse
Affiliation(s)
- Himanshu Polara
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Tejas Shah
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Godwin Babanyinah
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Hanghang Wang
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Abhi Bhadran
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Michael C Biewer
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Mihaela C Stefan
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| |
Collapse
|
7
|
Yang Y, Liu X, Zhang R, Liu Y, Zhou N, Jiang Y. Size-Tunable Micro-Nano Liposomes: Enhanced Lung Targeting and Tumor Penetration for Combination Treatment of Lung Cancer. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2409593. [PMID: 40237096 DOI: 10.1002/smll.202409593] [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: 10/17/2024] [Revised: 03/26/2025] [Indexed: 04/17/2025]
Abstract
The inefficient delivery of nanocarriers and drug resistance seriously limit therapeutic effects of lung cancer. Here, a size-tunable micro-nano liposome system, PCAL@TM, is designed for targeted delivery of paclitaxel (PTX) and oxygen to lung tumors. PTX-loaded corosolic acid (CA) nano-liposomes (PCAL, 100 nm) are anchored to the surface of oxygenated perfluorotributylamine (TBA)-loaded multivesicular liposomes (TM, 10 µm) via the biotin-avidin interactions with matrix metalloproteinase-9 (MMP-9) cleavable linker. After intravenous administration to lung tumor-bearing mice, the distribution amount of PCAL@TM in the lungs is extremely higher than that in the liver and spleen. The MMP-9-sensitive PCAL@TM can decouple into nano-PCAL and micro-TM in tumors; while, TMs enable breaking into smaller vesicles under vascular pressure, and release oxygen leading to the downregulation of HIF-1α and platelet-activated TGF-β. Meanwhile, PCAL can penetrate deeply into tumor by the tumor-targeted-penetrable CA liposomes, to promote the reduction of inflammation levels and enhance PTX-induced immunogenic cell death (ICD). Together, these results lead to the reversals of chemoresistance and tumor immunosuppressive, achieving significant improvement in PTX chemotherapy and α-PD-1 immunotherapy. The PCAL@TM system presents a novel strategy to enhance the efficiency of nano-drug delivery and the outcome of combined therapy for lung tumor.
Collapse
Affiliation(s)
- Yueying Yang
- Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China
| | - Xiao Liu
- Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China
| | - Ruizhe Zhang
- Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China
| | - Yunhu Liu
- Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China
| | - Nan Zhou
- Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China
| | - Yanyan Jiang
- Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China
| |
Collapse
|
8
|
Wang Y, Huang R, Feng S, Mo R. Advances in nanocarriers for targeted drug delivery and controlled drug release. Chin J Nat Med 2025; 23:513-528. [PMID: 40383609 DOI: 10.1016/s1875-5364(25)60861-2] [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: 08/23/2024] [Revised: 09/13/2024] [Accepted: 12/24/2024] [Indexed: 05/20/2025]
Abstract
Nanocarrier-based drug delivery systems (nDDSs) present significant opportunities for improving disease treatment, offering advantages in drug encapsulation, solubilization, stability enhancement, and optimized pharmacokinetics and biodistribution. nDDSs, comprising lipid, polymeric, protein, and inorganic nanovehicles, can be guided by or respond to biological cues for precise disease treatment and management. Equipping nanocarriers with tissue/cell-targeted ligands enables effective navigation in complex environments, while functionalization with stimuli-responsive moieties facilitates site-specific controlled release. These strategies enhance drug delivery efficiency, augment therapeutic efficacy, and reduce side effects. This article reviews recent strategies and ongoing advancements in nDDSs for targeted drug delivery and controlled release, examining lesion-targeted nanomedicines through surface modification with small molecules, peptides, antibodies, carbohydrates, or cell membranes, and controlled-release nanocarriers responding to endogenous signals such as pH, redox conditions, enzymes, or external triggers like light, temperature, and magnetism. The article also discusses perspectives on future developments.
Collapse
Affiliation(s)
- Yuqian Wang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Renqi Huang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Shufan Feng
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Ran Mo
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
| |
Collapse
|
9
|
Tiwari R, Dev D, Thalla M, Aher VD, Mundada AB, Mundada PA, Vaghela K. Nano-enabled pharmacogenomics: revolutionizing personalized drug therapy. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2025; 36:913-938. [PMID: 39589779 DOI: 10.1080/09205063.2024.2431426] [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: 08/12/2024] [Accepted: 11/07/2024] [Indexed: 11/27/2024]
Abstract
The combination of pharmacogenomics and nanotechnology science of pharmacogenomics into a highly advanced single entity has given birth to personalized medicine known as nano-enabled pharmacogenomics. This review article covers all aspects starting from pharmacogenomics to gene editing tools, how these have evolved or are likely to be evolved for pharmacogenomic application, and how these can be delivered using nanoparticle delivery systems. In this prior work, we explore the evolution of pharmacogenomics over the years, as well as new achievements in the field of genomic sciences, the challenges in drug creation, and application of the strategy of personalized medicine. Particular attention is paid to how nanotechnology helps avoid the problems that accompanied the development of pharmacogenomics earlier, for example, the question of drug resistance and targeted delivery. We also review the latest developments in nano-enabled pharmacogenomics, such as the coupling with other nanobio-technologies, artificial intelligence, and machine learning in pharmacogenomics, and the ethical and regulatory aspects of these developing technologies. The possible uses of nanotechnology in improving the chances of pated and treating drug-resistant cancers are exemplified by case studies together with the current clinical uses of nanotechnology. In the last section, we discuss the future trends and research prospects in this dynamically growing area, stressing the importance of further advancements and collaborations which will advance the nano-enabled pharmacogenomics to their maximum potential.
Collapse
Affiliation(s)
- Ruchi Tiwari
- Psit-Pranveer Singh Institute of Technology (Pharmacy), Kanpur-Agra-Delhi National, Kanpur, India
| | - Dhruv Dev
- Department of Pharmacy, Shivalik College of Pharmacy Nangal, Rupnagar, India
| | - Maharshi Thalla
- Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, Kingsville, TX, USA
| | - Vaibhav Dagaji Aher
- Department of Pharmaceutical Medicine, Maharashtra University of Health Sciences, Nashik, India
| | - Anand Badrivishal Mundada
- Department of Pharmacy, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India
| | | | - Krishna Vaghela
- Department of Pharmacy, Saraswati Institute of Pharmaceutical Sciences, National Forensic Sciences University, Gandhinagar, India
| |
Collapse
|
10
|
Mordzińska-Rak A, Telejko I, Adamczuk G, Trombik T, Stepulak A, Błaszczak E. Advancing Head and Neck Cancer Therapies: From Conventional Treatments to Emerging Strategies. Biomedicines 2025; 13:1046. [PMID: 40426875 PMCID: PMC12108569 DOI: 10.3390/biomedicines13051046] [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: 03/13/2025] [Revised: 04/16/2025] [Accepted: 04/22/2025] [Indexed: 05/29/2025] Open
Abstract
Head and neck cancers (HNCs), particularly head and neck squamous cell carcinoma (HNSCC), are among the most aggressive and prevalent malignancies of the upper aerodigestive tract. As the incidence of HNCs continues to rise, this cancer type presents a significant public health challenge. Despite conventional treatment options, such as surgery, chemotherapy, and radiotherapy, the five-year survival rates remain relatively low due to resistance to these therapies, local recurrence, local lymph node metastasis, and in some advanced cases also distant metastasis. Consequently, patients with HNCs face a high mortality risk and have reduced quality of life due to the side effects of chemo- and radiotherapy. Furthermore, targeted therapies and immunotherapies have also shown limited effectiveness in many cases, with issues related to resistance and the accessibility of these treatments. Therefore, new strategies, such as those based on combination therapies and nanotechnology, are being explored to improve the treatment of HNC patients. The proteolysis-targeting chimeras (PROTACs) also emerged as a promising therapeutic approach, though research is still ongoing to bring this technology into clinical practice. Here, we aim to highlight the current knowledge of HNC therapies, with a focus on recent advancements, including nanomedicine and PROTAC-based strategies. The development and advancement of novel emerging therapies hold promise for the improvement of patients' survival and quality of life.
Collapse
Affiliation(s)
- Aleksandra Mordzińska-Rak
- Department of Biochemistry and Molecular Biology, Faculty of Medical Sciences, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland
| | - Ilona Telejko
- Department of Biochemistry and Molecular Biology, Faculty of Medical Sciences, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland
| | - Grzegorz Adamczuk
- Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, 8b Jaczewski Street, 20-093 Lublin, Poland
| | - Tomasz Trombik
- Department of Biochemistry and Molecular Biology, Faculty of Medical Sciences, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland
| | - Andrzej Stepulak
- Department of Biochemistry and Molecular Biology, Faculty of Medical Sciences, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland
| | - Ewa Błaszczak
- Department of Biochemistry and Molecular Biology, Faculty of Medical Sciences, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland
| |
Collapse
|
11
|
Saladino GM, Mangarova DB, Nernekli K, Wang J, Annio G, Varniab ZS, Khatoon Z, Ribeiro Morais G, Shi Y, Chang E, Pisani LJ, Tikhomirov G, Falconer RA, Daldrup-Link HE. Multimodal imaging approach to track theranostic nanoparticle accumulation in glioblastoma with magnetic resonance imaging and intravital microscopy. NANOSCALE 2025; 17:9986-9995. [PMID: 40135284 PMCID: PMC11937943 DOI: 10.1039/d5nr00447k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 03/18/2025] [Indexed: 03/27/2025]
Abstract
Theranostic nanoparticles (NPs) have been designed for simultaneous therapeutic and diagnostic purposes, thereby enabling personalized cancer therapy and in vivo drug tracking. However, studies thus far have focused on imaging NP tumor accumulation at the macroscopic level and correlating results with ex vivo histology. Limited evidence exists on whether in vivo NP tumor contrast enhancement on magnetic resonance imaging (MRI) correlates with in vivo NP tumor accumulation at the microscopic level. To address this gap, the purpose of our study was to correlate quantitative MRI estimates of NP accumulation with in vivo NP signal quantification as measured through two-photon intravital microscopy (IVM) in an orthotopic murine glioblastoma multiforme model (GBM). To enable multimodal imaging, we designed dual-mode NPs, composed of a carbohydrate-coated magnetic core (Ferumoxytol) as an MRI contrast agent, and a conjugated fluorophore (FITC) for IVM detection. We administered these NPs with or without a conjugated vascular disrupting agent (VDA) to assess its effect on NP delivery to GBM. We correlated in vivo MRI contrast enhancement in tumors, quantified as T2 relaxation time, with IVM fluorescence spatial decay rate. Results demonstrated a significantly lower tumor T2 relaxation time and spatial decay rate in tumors targeted with VDA-conjugated NPs compared to unconjugated NPs. Postmortem histological analyses validated the in vivo observations. The presented multimodal imaging approach enabled a quantitative correlation between MRI contrast enhancement at the macroscopic level and NP accumulation in the tumor microenvironment. These studies lay the groundwork for the precise evaluation of the tumor targeting of theranostic NPs.
Collapse
Affiliation(s)
| | - Dilyana B Mangarova
- Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
| | - Kerem Nernekli
- Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
| | - Jie Wang
- Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
| | - Giacomo Annio
- Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
| | - Zahra Shokri Varniab
- Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
| | - Zubeda Khatoon
- Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK
| | - Goreti Ribeiro Morais
- Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK
| | - Yifeng Shi
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, 94720, USA
| | - Edwin Chang
- Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
| | - Laura J Pisani
- Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
| | - Grigory Tikhomirov
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, 94720, USA
| | - Robert A Falconer
- Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK
| | - Heike E Daldrup-Link
- Department of Radiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
| |
Collapse
|
12
|
Yang Z, Lyu J, Qian J, Wang Y, Liu Z, Yao Q, Chen T, Cao Y, Xie J. Glutathione: a naturally occurring tripeptide for functional metal nanomaterials. Chem Sci 2025; 16:6542-6572. [PMID: 40134663 PMCID: PMC11931393 DOI: 10.1039/d4sc08599j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 03/08/2025] [Indexed: 03/27/2025] Open
Abstract
Glutathione (GSH), a naturally occurring tripeptide, plays an important role as an intracellular antioxidant in the physiological microenvironment and participates in redox balance, detoxification, and cellular and disease regulation. The unique structural features of GSH, including the reductive thiol and multiple coordination sites (carboxyl and amino group), make it a significant molecule not only in the physiological context but also as a ligand in the development of functional metal nanomaterials. In this context, GSH's role as a protective ligand and reducing agent in surface etching and ligand exchange reactions has been explored at the molecular level, expanding the diversity of GSH-protected metal nanomaterials. With photoluminescence (PL) as one of its most intriguing properties, investigations into GSH's influence on PL properties emphasize its multifaceted coordination capabilities in surface coating, charge transfer from electron-rich functional groups, chirality arising from its unique structure, and available conjugation sites. Moreover, the biocompatibility of GSH, combined with the synergistic effect of metal components, renders GSH-protected nanomaterials an "Inseparable Duo" highly suited for applications in bio-sensing, bio-imaging via PL radiative decay and anti-cancer bio-therapies through photothermal therapy, photodynamic therapy, and radiotherapy. By exploring the multifaceted roles of GSH, this Perspective aims to highlight pathways including the encouragement of deeper synthetic exploration, innovative design at the bio-nano interface, and expanded nanobiomedical applications.
Collapse
Affiliation(s)
- Zhucheng Yang
- Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University Fuzhou 350207 P. R. China
- Department of Chemical and Biomolecular Engineering, National University of Singapore Singapore 117585 Singapore
| | - Jingkuan Lyu
- Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University Fuzhou 350207 P. R. China
- Department of Chemical and Biomolecular Engineering, National University of Singapore Singapore 117585 Singapore
| | - Jing Qian
- Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University Fuzhou 350207 P. R. China
- Department of Chemical and Biomolecular Engineering, National University of Singapore Singapore 117585 Singapore
| | - Yifan Wang
- Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University Fuzhou 350207 P. R. China
- Department of Chemical and Biomolecular Engineering, National University of Singapore Singapore 117585 Singapore
| | - Zhenghan Liu
- Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University Fuzhou 350207 P. R. China
- Department of Chemical and Biomolecular Engineering, National University of Singapore Singapore 117585 Singapore
| | - Qiaofeng Yao
- Key Laboratory of Organic Integrated Circuits, Ministry of Education, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin University Tianjin 300072 P. R. China
- Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) Tianjin 300072 P. R. China
| | - Tiankai Chen
- School of Science and Engineering, The Chinese University of Hong Kong (Shenzhen) Shenzhen 518172 P. R. China
| | - Yitao Cao
- National and Local Joint Engineering Research Center of MPTES in High Energy and Safety LIBs, Engineering Research Center of MTEES (Ministry of Education), Key Lab. of ETESPG (GHEI), South China Normal University Guangzhou 510006 P. R. China
| | - Jianping Xie
- Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University Fuzhou 350207 P. R. China
- Department of Chemical and Biomolecular Engineering, National University of Singapore Singapore 117585 Singapore
| |
Collapse
|
13
|
Parveen S, Konde DV, Paikray SK, Tripathy NS, Sahoo L, Samal HB, Dilnawaz F. Nanoimmunotherapy: the smart trooper for cancer therapy. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2025; 6:1002308. [PMID: 40230883 PMCID: PMC11996242 DOI: 10.37349/etat.2025.1002308] [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: 11/29/2024] [Accepted: 03/20/2025] [Indexed: 04/16/2025] Open
Abstract
Immunotherapy has gathered significant attention and is now a widely used cancer treatment that uses the body's immune system to fight cancer. Despite initial successes, its broader clinical application is hindered by limitations such as heterogeneity in patient response and challenges associated with the tumor immune microenvironment. Recent advancements in nanotechnology have offered innovative solutions to these barriers, providing significant enhancements to cancer immunotherapy. Nanotechnology-based approaches exhibit multifaceted mechanisms, including effective anti-tumor immune responses during tumorigenesis and overcoming immune suppression mechanisms to improve immune defense capacity. Nanomedicines, including nanoparticle-based vaccines, liposomes, immune modulators, and gene delivery systems, have demonstrated the ability to activate immune responses, modulate tumor microenvironments, and target specific immune cells. Success metrics in preclinical and early clinical studies, such as improved survival rates, enhanced tumor regression, and elevated immune activation indices, highlight the promise of these technologies. Despite these achievements, several challenges remain, including scaling up manufacturing, addressing off-target effects, and navigating regulatory complexities. The review emphasizes the need for interdisciplinary approaches to address these barriers, ensuring broader clinical adoption. It also provides insights into interdisciplinary approaches, advancements, and the transformative potential of nano-immunotherapy and promising results in checkpoint inhibitor delivery, nanoparticle-mediated photothermal therapy, immunomodulation as well as inhibition by nanoparticles and cancer vaccines.
Collapse
Affiliation(s)
- Suphiya Parveen
- Department of Biotechnology and Genetics, School of Sciences, Jain (Deemed-to-be-University), Bengaluru 560027, Karnataka, India
| | - Dhanshree Vikrant Konde
- Department of Biotechnology and Genetics, School of Sciences, Jain (Deemed-to-be-University), Bengaluru 560027, Karnataka, India
| | - Safal Kumar Paikray
- School of Biotechnology, Centurion University of Technology and Management, Jatni 752050, Odisha, India
| | - Nigam Sekhar Tripathy
- School of Biotechnology, Centurion University of Technology and Management, Jatni 752050, Odisha, India
| | - Liza Sahoo
- School of Biotechnology, Centurion University of Technology and Management, Jatni 752050, Odisha, India
| | - Himansu Bhusan Samal
- School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Jatni 752050, Odisha, India
| | - Fahima Dilnawaz
- School of Biotechnology, Centurion University of Technology and Management, Jatni 752050, Odisha, India
| |
Collapse
|
14
|
Yoshino Y, Yoshino F, Aoki I, Mori Y, Suzuki G, Tsuji S, Amano T, Shiino A, Chano T, Furusho Y, Murakami T, Yamazaki H, Yamada K. 2-Nitroimidazole-Functionalized Superparamagnetic Iron Oxide Nanoparticles Detect Hypoxic Regions of Glioblastomas on MRI and Improve Radiotherapy Efficacy. ACS NANO 2025; 19:12762-12776. [PMID: 40139197 PMCID: PMC11984306 DOI: 10.1021/acsnano.4c06753] [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: 05/21/2024] [Revised: 03/10/2025] [Accepted: 03/11/2025] [Indexed: 03/29/2025]
Abstract
The presence of hypoxic regions in tumors is associated with malignancy and is an important target for the high-precision diagnosis and treatment of tumors. Radioresistant hypoxic regions can be precisely identified and treated without the use of high doses of radiation if hypoxic region-specific contrast agents have a therapeutic effect. In this study, we synthesized a therapeutic-diagnostic complex agent (SPION-PG-NI) by combining polyglycerol-functionalized superparamagnetic iron oxide nanoparticles (SPION-PG, core diameter of 8.8 ± 1.9 nm) as an MRI contrast agent and 2-nitroimidazole (NI, a pimonidazole derivative) as a hypoxia-targeted ligand to visually evaluate hypoxic regions using MRI and improve radiotherapy efficacy at those sites. SPION-PG-NI showed a concentration-dependent contrast effect and had significantly higher accumulation in subcutaneous glioblastomas than the control agent, SPION-PG, 24 h after administration. Immunohistological evaluations showed that the SPION-PG-NI-accumulated regions corresponded well to hypoxic regions. SPION-PG-NI showed neither migration into the brain parenchyma nor neurotoxicity. Both SPION-PG and SPION-PG-NI decrease reactive oxygen species (ROS); however, they improve radiotherapy efficacy in hypoxic glioblastoma cells due to cytotoxicity. This effect of SPION-PG-NI was significantly higher than that of SPION-PG (p < 0.01). After 12 Gy irradiation, the mean normalized glioblastoma tumor volume on day 38 in the SPION-PG-NI group (288%) was significantly lower than that in the control group (882%) (p < 0.05). Collectively, these findings suggest the potential of SPION-PG-NI as a useful and safe tumor theranostic nanodevice for hypoxic imaging and improving radiotherapy efficacy.
Collapse
Affiliation(s)
- Yuki Yoshino
- Department
of Radiology, Kyoto Prefectural University
of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
- Kansai
BNCT Medical Center, Educational Foundation
of Osaka Medical and Pharmaceutical University, 2-7 Daigakucho, Takatsuki Osaka 569-8686, Japan
| | - Fumi Yoshino
- Department
of Obstetrics and Gynecology, Shiga University
of Medical Science, Seta, Otsu 520-2192, Japan
- Mariko
Clinic, 13-5 Noji, Kusatsu 525-0059, Japan
| | - Ichio Aoki
- Institute
for Quantum Medical Science, National Institutes
for Quantum Science and Technology (QST), Anagawa 4-9-1, Inage 263-8555 Chiba, Japan
| | - Yasuyuki Mori
- Department
of Chemistry, Shiga University of Medical
Science, Otsu 520-2192, Japan
| | - Gen Suzuki
- Department
of Radiology, Kyoto Prefectural University
of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Shunichiro Tsuji
- Department
of Obstetrics and Gynecology, Shiga University
of Medical Science, Seta, Otsu 520-2192, Japan
| | - Tsukuru Amano
- Department
of Obstetrics and Gynecology, Shiga University
of Medical Science, Seta, Otsu 520-2192, Japan
| | - Akihiko Shiino
- Department
of Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu 520-2192, Japan
| | - Tokuhiro Chano
- Department
of Clinical Laboratory Medicine, Shiga University
of Medical Science, Seta, Otsu 520-2192, Japan
| | - Yoshio Furusho
- Department
of Chemistry, Shiga University of Medical
Science, Otsu 520-2192, Japan
| | - Takashi Murakami
- Department
of Obstetrics and Gynecology, Shiga University
of Medical Science, Seta, Otsu 520-2192, Japan
| | - Hideya Yamazaki
- Department
of Radiology, Kyoto Prefectural University
of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Kei Yamada
- Department
of Radiology, Kyoto Prefectural University
of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| |
Collapse
|
15
|
Belyaev IB, Griaznova OY, Yaremenko AV, Deyev SM, Zelepukin IV. Beyond the EPR effect: Intravital microscopy analysis of nanoparticle drug delivery to tumors. Adv Drug Deliv Rev 2025; 219:115550. [PMID: 40021012 DOI: 10.1016/j.addr.2025.115550] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 02/18/2025] [Accepted: 02/18/2025] [Indexed: 03/03/2025]
Abstract
Delivery of nanoparticles (NPs) to solid tumors has long relied on enhanced permeability and retention (EPR) effect, involving permeation of NPs through a leaky vasculature with prolonged retention by reduced lymphatic drainage in tumor. Recent research studies and clinical data challenge EPR concept, revealing alternative pathways and approaches of NP delivery. The area was significantly impacted by the implementation of intravital optical microscopy, unraveling delivery mechanisms at cellular level in vivo. This review presents analysis of the reasons for EPR heterogeneity in tumors and describes non-EPR based concepts for drug delivery, which can supplement the current paradigm. One of the approaches is targeting tumor endothelium by NPs with subsequent intravascular drug release and gradient-driven drug transport to tumor interstitium. Others exploit various immune cells for tumor infiltration and breaking endothelial barriers. Finally, we discuss the involvement of active transcytosis through endothelial cells in NP delivery. This review aims to inspire further understanding of the process of NP extravasation in tumors and provide insights for developing next-generation nanomedicines with improved delivery.
Collapse
Affiliation(s)
- Iaroslav B Belyaev
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia; Eindhoven University of Technology, Eindhoven 5600 MB, the Netherlands
| | - Olga Yu Griaznova
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia
| | | | - Sergey M Deyev
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia
| | - Ivan V Zelepukin
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 75123, Sweden.
| |
Collapse
|
16
|
Liu Y, Xie Y, Chen Y, Duan J, Bao C, Wang J, Feng H, Wang M, Ren Y, Li P, Luo Q, Xu J, Jiang M, Men Y, Wu Y, Li J, Wang G, Lu W. A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice. Nat Commun 2025; 16:2854. [PMID: 40128211 PMCID: PMC11933685 DOI: 10.1038/s41467-025-57965-6] [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: 06/24/2023] [Accepted: 03/07/2025] [Indexed: 03/26/2025] Open
Abstract
Immune checkpoint blockade therapy using programmed cell death 1 (PD1) or programmed death ligand 1 (PD-L1) has made significant progress in the treatment of advanced cancers, with some patients achieving long-term remission without clinical recurrence. However, only a minority of colon cancer patients respond to the therapy. Here, we report a protease-cleavable anti-PD-L1 antibody liposome, eLipo anti-PD-L1, for enhancing colon cancer therapy. In vivo, eLipo anti-PD-L1 is cleaved by legumain at colon cancer site into pegylated anti-PD-L1 and cancer-homing doxorubicin liposome. Functional assessments show cancer-targeting, legumain-responding, tumor-penetrating, and immune-activating effects, as well as efficacy in treating colon cancer-bearing mice in vivo. Further mechanistic analysis implicates genes related to T cell differentiation and T cell receptor signaling as potential molecular mediators. Lastly, human colorectal cancer tissue evaluations verify expressions of PD-L1 and legumain, hinting a potential translatability. Our study thus suggests that eLipo anti-PD-L1 may be a feasible vector for co-delivery of immunochemotherapy for colon cancer.
Collapse
Affiliation(s)
- Yixuan Liu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Ying Xie
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Yuling Chen
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Jialun Duan
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Chunjie Bao
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Jinling Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Hexuan Feng
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Mengjie Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Yuxin Ren
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Peishan Li
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Qian Luo
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Jiarui Xu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Min Jiang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Yanchen Men
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Yang Wu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Jianwei Li
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Guiling Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Wanliang Lu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China.
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China.
| |
Collapse
|
17
|
Della Pelle G, Markelc B, Bozic T, Šribar J, Krizaj I, Zagar Soderznik K, Hudoklin S, Kreft ME, Urbančič I, Kisovec M, Podobnik M, Kostevšek N. Red Blood Cell Membrane Vesicles for siRNA Delivery: A Biocompatible Carrier With Passive Tumor Targeting and Prolonged Plasma Residency. Int J Nanomedicine 2025; 20:3269-3301. [PMID: 40109366 PMCID: PMC11921803 DOI: 10.2147/ijn.s504644] [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: 11/04/2024] [Accepted: 02/04/2025] [Indexed: 03/22/2025] Open
Abstract
Background Despite many advances in gene therapy, the delivery of small interfering RNAs is still challenging. Erythrocytes are the most abundant cells in the human body, and their membrane possesses unique features. From them, erythrocytes membrane vesicles can be generated, employable as nano drug delivery system with prolonged blood residence and high biocompatibility. Methods Human erythrocyte ghosts were extruded in the presence of siRNA, and the objects were termed EMVs (erythrocyte membrane vesicles). An ultracentrifugation-based method was applied to select only the densest EMVs, ie, those containing siRNA. We evaluated their activity in vitro in B16F10 cells expressing fluorescent tdTomato and in vivo in B16F10 tumor-bearing mice after a single injection. Results The EMVs had a negative zeta potential, a particle size of 170 nm and excellent colloidal stability after one month of storage. With 0.3 nM siRNA, more than 75% gene knockdown was achieved in vitro, and 80% was achieved in vivo, at 2 days PI at 2.5 mg/kg. EMVs mostly accumulate around blood vessels in the lungs, brain and tumor. tdTomato fluorescence steadily decreased in tumor areas with higher EMVs concentration, which indicates efficient gene knockdown. Approximately 2% of the initial dose of EMVs was still present in the plasma after 2 days. Conclusion The entire production process of the purified siRNA-EMVs took approximately 4 hours. The erythrocyte marker CD47 offered protection against macrophage recognition in the spleen and in the blood. The excellent biocompatibility and pharmacokinetic properties of these materials make them promising platforms for future improvements, ie, active targeting and codelivery with conventional chemotherapeutics.
Collapse
Affiliation(s)
- Giulia Della Pelle
- Department for Nanostructured Materials, Jožef Stefan Institute, Ljubljana, 1000, Slovenia
- Jožef Stefan International Postgraduate School, Ljubljana, 1000, Slovenia
| | - Bostjan Markelc
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, 1000, Slovenia
| | - Tim Bozic
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, 1000, Slovenia
| | - Jernej Šribar
- Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, 1000, Slovenia
| | - Igor Krizaj
- Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, 1000, Slovenia
| | | | - Samo Hudoklin
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia
| | - Mateja Erdani Kreft
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia
| | - Iztok Urbančič
- Laboratory of Biophysics, Condensed Matter Physics Department, Jožef Stefan Institute, Ljubljana, 1000, Slovenia
| | - Matic Kisovec
- Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, 1000, Slovenia
| | - Marjetka Podobnik
- Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, 1000, Slovenia
| | - Nina Kostevšek
- Department for Nanostructured Materials, Jožef Stefan Institute, Ljubljana, 1000, Slovenia
| |
Collapse
|
18
|
Yu Y, Li W, Yu Q, Ye J, Wang H, Li Y, Yin S. Biomimetic-Nanoparticle-Enhanced Photothermal Immunotherapy: Targeted Delivery of Near-Infrared Region II Agents and Immunoadjuvants for Tumor Immunogenicity. Biomater Res 2025; 29:0151. [PMID: 40040955 PMCID: PMC11876542 DOI: 10.34133/bmr.0151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/02/2025] [Accepted: 01/31/2025] [Indexed: 03/06/2025] Open
Abstract
Advancing at the cutting edge of oncology, the synergistic application of photothermal therapy coupled with immunotherapy is rapidly establishing itself as an innovative and potent strategy against cancer. A critical challenge in this domain is the precise and efficient targeting of tumor tissues with photothermal agents and immunoadjuvants while minimizing interference with healthy tissues. In this paper, we introduce an ingenious biomimetic nanoparticle platform, cancer cell membrane coated F127/(R837 and IR1048) (CFRI) nanoparticles encapsulating a near-infrared region II photothermal agent, IR1048, and an immunostimulatory molecule, R837, with their surface modified using membranes derived from tumor cells, conferring exceptional specificity for tumor targeting. CFRI nanoparticles demonstrated an extraordinary photothermal conversion efficiency of 49%, adeptly eradicating in situ tumors. This process also triggered the release of damage-associated molecular patterns, thereby activating dendritic cells and catalyzing the maturation and differentiation of T cells, initiating a robust immune response. In vivo animal models substantiated that the CFRI-mediated synergistic photothermal and immunotherapeutic strategy markedly suppressed the proliferation of in situ tumors and provoked a vigorous systemic immune response, effectively curtailing the metastasis and recurrence of distant tumors. The successful development of the CFRI nanoparticle system offers a promising horizon for future clinical translations and pioneering research in oncology.
Collapse
Affiliation(s)
- Yanlu Yu
- Key Laboratory of Organosilicon Chemistry and Materials Technology of Ministry of Education, College of Materials, Chemistry and Chemical Engineering,
Hangzhou Normal University, 311121 Hangzhou, P. R. China
| | - Wen Li
- Key Laboratory of Organosilicon Chemistry and Materials Technology of Ministry of Education, College of Materials, Chemistry and Chemical Engineering,
Hangzhou Normal University, 311121 Hangzhou, P. R. China
| | - Qiqi Yu
- Key Laboratory of Organosilicon Chemistry and Materials Technology of Ministry of Education, College of Materials, Chemistry and Chemical Engineering,
Hangzhou Normal University, 311121 Hangzhou, P. R. China
| | - Jingtao Ye
- Key Laboratory of Organosilicon Chemistry and Materials Technology of Ministry of Education, College of Materials, Chemistry and Chemical Engineering,
Hangzhou Normal University, 311121 Hangzhou, P. R. China
| | - Hu Wang
- Key Laboratory of Ageing and Cancer Biology of Zhejiang Province, Institute of Ageing Research, School of Medicine,
Hangzhou Normal University, 311121 Hangzhou, P. R. China
| | - Yang Li
- Key Laboratory of Organosilicon Chemistry and Materials Technology of Ministry of Education, College of Materials, Chemistry and Chemical Engineering,
Hangzhou Normal University, 311121 Hangzhou, P. R. China
| | - Shouchun Yin
- Key Laboratory of Organosilicon Chemistry and Materials Technology of Ministry of Education, College of Materials, Chemistry and Chemical Engineering,
Hangzhou Normal University, 311121 Hangzhou, P. R. China
| |
Collapse
|
19
|
Hussein L, Moaness M, Mabrouk M, Farahat MG, Beherei HH. Advancements in mesoporous bioactive glasses for effective bone cancer therapy: Recent developments and future perspectives. BIOMATERIALS AND BIOSYSTEMS 2025; 17:100108. [PMID: 40083816 PMCID: PMC11904600 DOI: 10.1016/j.bbiosy.2025.100108] [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: 12/30/2024] [Revised: 02/04/2025] [Accepted: 02/14/2025] [Indexed: 03/16/2025] Open
Abstract
This review focuses on recent advancements in the effective use of mesoporous bioactive glasses (MBG) in the treatment of bone cancer, focusing on Osteosarcoma (OS). Bone cancers are rare but are associated with significant morbidity and mortality; often, aggressive treatment is required. Conventional treatments such as surgery, radiation, and chemotherapy are often not enough. This is because surgery cannot completely remove the tumor, without creating a critical size which are defects larger than 2 cm that cannot be repaired by physiological mechanisms. As a result, patients often face the additional burden of radiation and chemotherapy. Scientists have been exploring new treatments, including hyperthermia-targeted therapy, polymeric nanoparticles, and stem cell therapy. This could potentially negatively impact healthy tissues and organs. MBG offers a promising alternative to chemotherapeutic agents and ions for disease treatment as it acts as a multifunctional drug delivery system (DDS). In addition, MBG can also be engineered into scaffolds to facilitate local delivery of growth factors and drugs, thus promoting the efficiency of bone healing and restoration. Therefore, the current review highlights various MBG types reported in the past decade and explores potential future paths to enhance their use in bone cancer treatment while also giving insight on the already commercially available BGs that are used in different bone-related disease.
Collapse
Affiliation(s)
- Laila Hussein
- Refractories, Ceramics and Building Materials Department, Advanced Materials, Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt
| | - Mona Moaness
- Refractories, Ceramics and Building Materials Department, Advanced Materials, Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt
| | - Mostafa Mabrouk
- Refractories, Ceramics and Building Materials Department, Advanced Materials, Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt
| | - Mohamed G. Farahat
- Botany and Microbiology Department, Faculty of Science, Cairo University, Giza, Egypt
- Biotechnology Department, Faculty of Postgraduate Studies for Nanotechnology, Sheikh Zayed Branch Campus, Cairo University, Sheikh Zayed City 12588, Egypt
| | - Hanan H. Beherei
- Refractories, Ceramics and Building Materials Department, Advanced Materials, Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt
| |
Collapse
|
20
|
Wang X, Allen C. Synergistic effects of thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy in breast cancer management: an orthotopic mouse model study. Drug Deliv Transl Res 2025; 15:1011-1022. [PMID: 38977541 DOI: 10.1007/s13346-024-01654-2] [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] [Accepted: 06/13/2024] [Indexed: 07/10/2024]
Abstract
Liposome formulations of the cancer drug doxorubicin have been developed to address the severe side effects that result from administration of this drug in a conventional formulation. Among them, thermosensitive liposomal doxorubicin presents enhanced tumor targeting and efficient drug release when combined with mild hyperthermia localized to the tumor site. Exploiting the radiosensitizing benefits of localized thermal therapy, the integration of radiation therapy with the thermally activated liposomal system is posited to amplify the anti-tumor efficacy. This study explored a synergistic therapeutic strategy that combines thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy, using an orthotopic murine model of breast cancer. The protocol of sequential multi-modal treatment, incorporating low-dose chemotherapy and radiotherapy, substantially postponed the progression of primary tumor growth in comparison to the application of monotherapy at elevated dosages. Improvements in unheated distant lesions were also observed. Furthermore, the toxicity associated with the combination treatment was comparable to that of either thermosensitive liposome treatment or radiation alone at low doses. These outcomes underscore the potential of multi-modal therapeutic strategies to refine treatment efficacy while concurrently diminishing adverse effects in the management of breast cancer, providing valuable insight for the future refinement of thermosensitive liposomal doxorubicin applications.
Collapse
Affiliation(s)
- Xuehan Wang
- Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada
| | - Christine Allen
- Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.
- Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
| |
Collapse
|
21
|
Dang Z, Zheng X, Gao Y, Du Y, Zhang Y, Zhu S. In situ albumin tagging for targeted imaging of endothelial barrier disruption. SCIENCE ADVANCES 2025; 11:eads4412. [PMID: 39951533 PMCID: PMC11827639 DOI: 10.1126/sciadv.ads4412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 01/14/2025] [Indexed: 02/16/2025]
Abstract
The endothelial barrier (EB) is a critical component of the body's homeostatic mechanisms, thus developing effective imaging techniques to visualize its integrity is essential. The EB disruption is accompanied by the alternations in permeability and even the breakdown of tight junctions (TJs), leading to the leakage of albumin; thus, albumin can serve as a biomarker for EB disruption. Herein, we develop an albumin-specific, covalently tagged near-infrared II (NIR-II) dye, with its high selectivity for endogenous albumin, for targeted imaging EB disruption. Our albumin-tagging dye serves as a chromophore to construct NIR-II fluorescent proteins in situ, with substantially improved brightness. Thus, through in situ dye tagging of endogenous albumin as the efficient "targeting agent," we can precisely image disruptions in various endothelial barriers. Unlike the traditional exogenous targeting agents (e.g., dye-labeled antibodies) with enzymatic degradation or immune system capture issues, in situ albumin tagging demonstrates superhigh performance for targeted imaging.
Collapse
Affiliation(s)
- Zetao Dang
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P.R. China
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China
| | - Xue Zheng
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P.R. China
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China
| | - Yanli Gao
- Department of Pediatric Ultrasound, Ultrasound Diagnostic Center, The First Hospital of Jilin University, Changchun 130021, P.R. China
| | - Yijing Du
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P.R. China
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China
| | - Yuewei Zhang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China
| | - Shoujun Zhu
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P.R. China
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital of Jilin University, Changchun 130021, P.R. China
| |
Collapse
|
22
|
Tang L, Yang X, He L, Zhu C, Chen Q. Preclinical advance in nanoliposome-mediated photothermal therapy in liver cancer. Lipids Health Dis 2025; 24:31. [PMID: 39891269 PMCID: PMC11783920 DOI: 10.1186/s12944-024-02429-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/31/2024] [Indexed: 02/03/2025] Open
Abstract
Liver cancer is a highly lethal malignant tumor with a high incidence worldwide. Therefore, its treatment has long been a focus of medical research. Although traditional treatment methods such as surgery, radiotherapy, and chemotherapy have increased the survival rate of patients, their efficacy remains unsatisfactory owing to the nonspecific distribution of drugs, high toxicity, and drug resistance of tumor tissues. In recent years, the application of nanotechnology in the medical field has opened a new avenue for the treatment of liver cancer. Among these treatment methods, photothermal therapy (PTT) based on nanoliposomes has attracted wide attention owing to its unique targeting and high efficiency. This article reviews the latest preclinical research progress of nanoliposome-based PTT for liver cancer and its metastasis, discusses the preclinical challenges in this field, and proposes directions for improvement, with the aim of improving the effectiveness of liver cancer treatment.
Collapse
Affiliation(s)
- Lixuan Tang
- School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Xiao Yang
- The department of oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Liwen He
- School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Chaogeng Zhu
- The department of hepatobiliary pancreatic hernia surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410208, China.
| | - Qingshan Chen
- The department of hepatobiliary pancreatic hernia surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410208, China.
| |
Collapse
|
23
|
Malhotra A, Dehghankelishadi P, Kaur I, Marshall M, Rudd D, Wojnilowicz M, Nowell CJ, Fulcher AJ, Esser L, Tong WY, Cifuentes A, Wagstaff KM, Voelcker NH. Triple-Negative Breast Cancer Aptamer-Targeting Porous Silicon Nanocarrier. ACS APPLIED MATERIALS & INTERFACES 2025; 17:5955-5969. [PMID: 39804251 DOI: 10.1021/acsami.4c18453] [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: 01/31/2025]
Abstract
Common treatment approaches for triple-negative breast cancer (TNBC) are associated with severe side effects due to the unfavorable biodistribution profile of potent chemotherapeutics. Here, we explored the potential of TNBC-targeting aptamer-decorated porous silicon nanoparticles (pSiNPs) as targeted nanocarriers for TNBC. A "salt-aging" strategy was employed to fabricate a TNBC-targeting aptamer functionalized pSiNP that was highly colloidally stable. Doxorubicin (Dox) was efficiently loaded into nanoparticles (179 ± 5 μg/mg of pSiNP) and experienced pH-dependent release kinetics. Further experiments highlighted that clathrin-mediated endocytosis was the primary route that aptamer-pSiNP conjugates take to enter the endolysosomal compartment of the MCF10Ca1h TNBC cells. A time-interval colocalization study shows the accumulation of an aptamer-decorated pSiNP conjugate in the lysosomes of TNBC cells, unlike for antibody-decorated pSiNPs, leading to particle-induced lysosomal swelling and membrane destabilization. Dox-loaded aptamer-pSiNPs efficiently reduced the viability of the TNBC cells (11.8 ± 1.5%) compared to nontargeted nanoparticles (58.2 ± 8.8%) while the developed system showed a low level of toxicity in healthy cells, both in vitro and in vivo. These findings have laid the foundation for further investigating the potential of aptamer-pSiNP conjugates as a targeted treatment strategy in preclinical TNBC models.
Collapse
Affiliation(s)
- Ankit Malhotra
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
| | - Pouya Dehghankelishadi
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
| | - Ishdeep Kaur
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
| | - Morgan Marshall
- Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3168, Australia
| | - David Rudd
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
| | - Marcin Wojnilowicz
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
- Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria 3168, Australia
| | - Cameron J Nowell
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
| | - Alex J Fulcher
- Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3168, Australia
| | - Lars Esser
- Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria 3168, Australia
| | - Wing Yin Tong
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
| | - Anna Cifuentes
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
| | - Kylie M Wagstaff
- Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3168, Australia
| | - Nicolas H Voelcker
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
- Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria 3168, Australia
- Materials Science and Engineering, Monash University, 14 Alliance Lane, Clayton, Victoria 3168, Australia
- Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, 151 Wellington Road, Clayton, Victoria 3168, Australia
| |
Collapse
|
24
|
Li Y, Qu F, Wan F, Zhong C, Rao J, Liu Y, Li Z, Zhu J, Li Z. Aggregation control of anionic pentamethine cyanine enabling excitation wavelength selective NIR-II fluorescence imaging-guided photodynamic therapy. Nat Commun 2025; 16:762. [PMID: 39824804 PMCID: PMC11748625 DOI: 10.1038/s41467-024-55429-x] [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: 09/30/2023] [Accepted: 12/11/2024] [Indexed: 01/20/2025] Open
Abstract
Near-infrared (NIR)-II fluorescence imaging-guided photodynamic therapy (PDT) has shown great potential for precise diagnosis and treatment of tumors in deep tissues; however, its performance is severely limited by the undesired aggregation of photosensitizers and the competitive relationship between fluorescence emission and reactive oxygen species (ROS) generation. Herein, we report an example of an anionic pentamethine cyanine (C5T) photosensitizer for high-performance NIR-II fluorescence imaging-guided PDT. Through the counterion engineering approach, a triphenylphosphine cation (Pco) modified with oligoethylene glycol chain is synthesized and adopted as the counterion of C5T, which can effectively suppress the excessive and disordered aggregation of the resulting C5T-Pco by optimizing the dye amphipathicity and enhancing the cyanine-counterion interactions. Dynamic tuning of fluorescence characteristics and ROS generation is achieved at the aggregate level, resulting in an impressive type I ROS generation under 760 nm light irradiation, accompanied by efficient NIR-II fluorescence emission excited at 808 nm. As a result, excitation wavelength selective NIR-II fluorescence imaging-guided PDT has been successfully demonstrated for tumor diagnosis and therapeutics of female mice.
Collapse
Affiliation(s)
- Yibin Li
- Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology (HUST), Wuhan, China
| | - Fei Qu
- Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology (HUST), Wuhan, China
| | - Fang Wan
- Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology (HUST), Wuhan, China
| | - Cheng Zhong
- Department of Chemistry, Hubei Key Lab on Organic and Polymeric Optoelectronic Materials, Wuhan University, Wuhan, China
| | - Jingyi Rao
- Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology (HUST), Wuhan, China
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, HUST, Wuhan, China
| | - Yijing Liu
- Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology (HUST), Wuhan, China.
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, HUST, Wuhan, China.
| | - Zhen Li
- Department of Chemistry, Hubei Key Lab on Organic and Polymeric Optoelectronic Materials, Wuhan University, Wuhan, China
| | - Jintao Zhu
- Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology (HUST), Wuhan, China
- Hubei Key Laboratory of Material Chemistry and Service Failure, HUST, Wuhan, China
| | - Zhong'an Li
- Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology (HUST), Wuhan, China.
- Hubei Key Laboratory of Material Chemistry and Service Failure, HUST, Wuhan, China.
| |
Collapse
|
25
|
Ghorbani M, Prince E. Radical Ring-Opening Polymerization: Unlocking the Potential of Vinyl Polymers for Drug Delivery, Tissue Engineering, and More. Biomacromolecules 2025; 26:118-139. [PMID: 39733344 DOI: 10.1021/acs.biomac.4c01116] [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: 12/31/2024]
Abstract
Synthetic vinyl polymers have long been recognized for their potential to be utilized in drug delivery, tissue engineering, and other biomedical applications. The synthetic control that chemists have over their structure and properties is unmatched, allowing vinyl polymer-based materials to be precisely engineered for a range of therapeutic applications. Yet, their lack of biodegradability compromises the biocompatibility of vinyl polymers and has held back their translation into clinically used treatments for disease thus far. In recent years, radical ring-opening polymerization (rROP) has emerged as a promising strategy to render synthetic vinyl polymers biodegradable and bioresorbable. While rROP has long been touted as a strategy for preparing biodegradable vinyl polymers for biomedical applications, the translation of rROP into clinically approved treatments for disease has not yet been realized. This review highlights the opportunities for leveraging rROP to render vinyl polymers biodegradable and unlock their potential for use in biomedical applications.
Collapse
Affiliation(s)
- Mina Ghorbani
- Department of Chemical Engineering, University of Waterloo, 200 University Ave. WestN2L 3G1WaterlooON Canada
| | - Elisabeth Prince
- Department of Chemical Engineering, University of Waterloo, 200 University Ave. WestN2L 3G1WaterlooON Canada
- Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Ave. WestN2L 3G1WaterlooON Canada
| |
Collapse
|
26
|
Meher N, Bidkar AP, Wadhwa A, Bobba KN, Dhrona S, Dasari C, Mu C, Fong COY, Cámara JA, Ali U, Basak M, Bulkley D, Steri V, Fontaine SD, Zhu J, Oskowitz A, Aggarwal RR, Sriram R, Chou J, Wilson DM, Seo Y, Santi DV, Ashley GW, VanBrocklin HF, Flavell RR. PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer. Mol Cancer Ther 2025; 24:141-151. [PMID: 39331510 DOI: 10.1158/1535-7163.mct-24-0024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 04/05/2024] [Accepted: 09/25/2024] [Indexed: 09/29/2024]
Abstract
The enhanced permeability and retention (EPR) effect controls passive nanodrug uptake in tumors and may provide a high tumor payload with prolonged retention for cancer treatment. However, EPR-mediated tumor uptake and distribution vary by cancer phenotype. Thus, we hypothesized that a companion PET imaging surrogate may benefit EPR-mediated therapeutic drug delivery. We developed two 89Zr-radiolabeled nanocarriers based on 4-armed starPEG40kDa with or without talazoparib (TLZ), a potent PARP inhibitor, as surrogates for the PEG-TLZ4 therapeutic scaffold. For PET imaging, PEG-DFB4 and PEG-DFB1-TLZ3 were radiolabeled with 89Zr by replacing one or all four copis of TLZ on PEG-TLZ4 with deferoxamine B (DFB). The radiolabeled nanodrugs [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 were tested in vivo in prostate cancer subcutaneous (s.c.) xenografts (22Rv1, LTL-545, and LTL-610) and 22Rv1 metastatic models. Their EPR-mediated tumoral uptake and penetration was compared with CT26, a known EPR-high cell line. MicroPET/CT images, organ biodistribution, and calculated kinetic parameters showed high uptake in CT26 and LTL-545 and moderate to low uptake in LTL-610 and 22Rv1. MicroPET/CT and high-resolution autoradiographic images showed nanocarrier penetration into highly permeable CT26, but heterogeneous peripheral accumulation was observed in LTL-545, LTL-610, and 22Rv1 s.c. xenografts and metastatic tumors. CD31 staining of tumor sections showed homogenous vascular development in CT26 tumors and heterogeneity in other xenografts. Both [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 showed similar accumulation and distribution in s.c. and metastatic tumor models. Both nanocarriers can measure tumor model passive uptake heterogeneity. Although heterogeneous, prostate cancer xenografts had low EPR. These starPEG nanocarriers could be used as PET imaging surrogates to predict drug delivery and efficacy.
Collapse
Affiliation(s)
- Niranjan Meher
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
- National Institute of Pharmaceutical Education and Research, Lucknow, India
| | - Anil P Bidkar
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Anju Wadhwa
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Kondapa Naidu Bobba
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Suchi Dhrona
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Chandrashekhar Dasari
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
- Division of Vascular and Endovascular Surgery, University of California San Francisco, San Francisco, California
| | - Changhua Mu
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Cyril O Y Fong
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Juan A Cámara
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
| | - Umama Ali
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Megha Basak
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - David Bulkley
- Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California
| | - Veronica Steri
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
| | | | - Jun Zhu
- Department of Medicine, University of California San Francisco, San Francisco, California
| | - Adam Oskowitz
- Division of Vascular and Endovascular Surgery, University of California San Francisco, San Francisco, California
| | - Rahul R Aggarwal
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
| | - Renuka Sriram
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Jonathan Chou
- Department of Medicine, University of California San Francisco, San Francisco, California
| | - David M Wilson
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
| | - Youngho Seo
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
| | | | | | - Henry F VanBrocklin
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
| | - Robert R Flavell
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
- Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California
| |
Collapse
|
27
|
Wu Y, Shang J, Zhang X, Li N. Advances in molecular imaging and targeted therapeutics for lymph node metastasis in cancer: a comprehensive review. J Nanobiotechnology 2024; 22:783. [PMID: 39702277 PMCID: PMC11657939 DOI: 10.1186/s12951-024-02940-4] [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: 01/30/2024] [Accepted: 10/19/2024] [Indexed: 12/21/2024] Open
Abstract
Lymph node metastasis is a critical indicator of cancer progression, profoundly affecting diagnosis, staging, and treatment decisions. This review article delves into the recent advancements in molecular imaging techniques for lymph nodes, which are pivotal for the early detection and staging of cancer. It provides detailed insights into how these techniques are used to visualize and quantify metastatic cancer cells, resident immune cells, and other molecular markers within lymph nodes. Furthermore, the review highlights the development of innovative, lymph node-targeted therapeutic strategies, which represent a significant shift towards more precise and effective cancer treatments. By examining cutting-edge research and emerging technologies, this review offers a comprehensive overview of the current and potential impact of lymph node-centric approaches on cancer diagnosis, staging, and therapy. Through its exploration of these topics, the review aims to illuminate the increasingly sophisticated landscape of cancer management strategies focused on lymph node assessment and intervention.
Collapse
Affiliation(s)
- Yunhao Wu
- Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Jin Shang
- Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Xinyue Zhang
- The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Nu Li
- The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
| |
Collapse
|
28
|
Khaliq NU, Amin L, Khaliq SU, Amin A, Omer S, Khaliq IU, Kim Y, Kim J, Kim T, Seo D, Sung D, Kim H. Peptide-Based Prodrug Approaches for Cancer Nanomedicine. ACS APPLIED BIO MATERIALS 2024; 7:8163-8176. [PMID: 39601471 DOI: 10.1021/acsabm.4c01364] [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] [Indexed: 11/29/2024]
Abstract
Peptide-based prodrugs, such as peptide-drug conjugates (PDCs), are currently being developed for cancer therapy. PDCs are considered single-component nanomedicines with various functionalities. The peptide moieties provide stability to the PDCs, which self-assemble into nanostructures in an aqueous medium. Several PDCs based on peptide moieties have been developed for targeted cancer therapy, prevention of multidrug resistance (MDR), and theranostic applications. Based on this information, next-level strategies have been developed to deliver therapeutics and diagnostics to tumor tissues. The induction of apoptosis-targeted therapy is a conceptual approach that has evolved. In this context, smart PDCs have been designed and explored to overcome tumor heterogeneity. This review highlights strategies for the targeted delivery of small molecules and theranostic applications. Moreover, a conceptual approach to induce apoptosis-targeted therapy was exploited through the delivery of smart PDC nanomedicines and their composites.
Collapse
Affiliation(s)
- Nisar Ul Khaliq
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| | - Laraib Amin
- Northwest General Hospital and Research Center, Peshawar 25100, Pakistan
| | - Saad Ul Khaliq
- Northwest General Hospital and Research Center, Peshawar 25100, Pakistan
| | - Anam Amin
- Northwest General Hospital and Research Center, Peshawar 25100, Pakistan
| | - Samreen Omer
- Riphah International University, Islamabad 44000, Pakistan
| | | | - Yejin Kim
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| | - Joohyeon Kim
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| | - Taeho Kim
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| | - Dongseong Seo
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea
- Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic 5 Engineering and Technology, 202 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Daekyung Sung
- Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic 5 Engineering and Technology, 202 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Hyungjun Kim
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| |
Collapse
|
29
|
Yin M, Zhang X, Zhang T, Bao Z, He Z. Folic Acid-Targeted Mixed Pluronic Micelles for Delivery of Triptolide. Polymers (Basel) 2024; 16:3485. [PMID: 39771337 PMCID: PMC11677570 DOI: 10.3390/polym16243485] [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: 10/21/2024] [Revised: 12/11/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
The present study aimed to explore an ideal delivery system for triptolide (TPL) by utilizing the thin-film hydration method to prepare drug-loaded, folate-modified mixed pluronic micelles (FA-F-127/F-68-TPL). Scanning electron microscopy and atomic force microscopy showed that the drug-loaded micelles had a spherical shape with a small particle size, with an average of 30.7 nm. Cell viability experiments showed that FA-F-127/F-68-TPL significantly reduced HepG2 cell viability, exhibiting strong cytotoxicity. Its cytotoxicity was markedly enhanced compared with bare TPL. Nile red (Nr) was used as a model drug to prepare FA-F-127/F-68-Nr to further validate its tumor-targeting and cellular uptake capability. After coincubation with HepG2 cells, a multifunctional microplate reader showed that intracellular fluorescence intensity significantly increased, indicating that FA-F-127/F-68-Nr could more effectively enter the cells. A nude mouse model of subcutaneous hepatocellular carcinoma was constructed. Following tail vein injection of FA-F-127/F-68-Nr, the fluorescence imaging system showed that FA-F127/F-68-Nr could significantly target tumor tissue, and even if entering the small-sized tumor was challenging, it could be excreted through urine. Nude mice with subcutaneous hepatocellular carcinoma were treated with tail vein injections of FA-F-127/F-68-TPL (45 µg/kg) every other day for 21 days. The results showed that the growth of the transplanted tumors was significantly slowed, with no significant difference compared with bare TPL. In summary, the FA-F-127/F-68-TPL exhibits the advantages of low cost, excellent biological properties, active/passive targeting capabilities, notable cytotoxicity against liver cancer cells, and significant inhibition of transplanted hepatocellular carcinoma growth. Significantly, the FA-F-127/F-68-TPL, despite challenges in targeting tumors with an insignificant EPR effect, can be efficiently excreted via the kidneys, thereby preventing the release of the drug during prolonged circulation and potential damage to normal tissues. Therefore, FA-F-127/F-68-TPL represents a promising antitumor drug delivery system.
Collapse
Affiliation(s)
- Meizhen Yin
- Medical College, Inner Mongolia Minzu University, Tongliao 028043, China
| | | | | | | | | |
Collapse
|
30
|
Ando T, Vu TN, Nishimura T, Takahashi R, Yusa SI. Synthesis and Characterization of Polyion Complex Micelles with Glycopolymer Shells for Drug Delivery Carriers. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2024; 40:26249-26258. [PMID: 39591594 DOI: 10.1021/acs.langmuir.4c03795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2024]
Abstract
Double hydrophilic diblock copolymers (G20A100 and G100A98), composed of non-charged poly(glycosyloxyethyl methacrylate) (PGEMA, G) and cationic poly((3-acrylamidopropyl)trimethylammonium chloride), were synthesized via reversible addition-fragementation chain transfer (RAFT) radical polymerization. Likewise, diblock copolymers (G20S80 and G100S78), composed of PGEMA and anionic poly(2-acrylamido-2-methylpropanesulfonate) were synthesized via RAFT. The subscripts in these abbreviations indicate the degree of polymerization (DP) of each block. Polyion complex (PIC) aggregates (G20A100/G20S80 and G100A98/G100S78) were formed through electrostatic interactions by combining oppositely charged diblock copolymers with matched DPs for charge neutralization. The hydrodynamic radii of the G20A100/G20S80 and G100A98/G100S78 PIC aggregates were 77.4 and 26.2 nm, respectively, with zeta potentials close to 0 mV. The G20A100/G20S80 PIC micelles tend to form intermicellar aggregates, resulting in an increase in the particle size over time. In contrast, G100A98/G100S78 PIC micelles exhibited colloidal stability with a constant spherical core-shell shape, which was unaffected by time. The morphology and stability of the PIC aggregates depend upon the DP ratio of PGEMA and oppositely charged polyelectrolyte blocks. Both G20A100/G20S80 and G100A98/G100S78 PIC aggregates dissociated above 0.8 M NaCl due to the screening effect of NaCl.
Collapse
Affiliation(s)
- Tomoki Ando
- Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan
| | - Thi Ngan Vu
- Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan
| | - Tomoya Nishimura
- Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan
| | - Rintaro Takahashi
- Department of Macromolecular Science, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan
| | - Shin-Ichi Yusa
- Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan
| |
Collapse
|
31
|
Araie H, Hosono N, Yamauchi T. Cellular uptake of CPX-351 by scavenger receptor class B type 1-mediated nonendocytic pathway. Exp Hematol 2024; 140:104651. [PMID: 39362576 DOI: 10.1016/j.exphem.2024.104651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 08/23/2024] [Accepted: 09/02/2024] [Indexed: 10/05/2024]
Abstract
The proper uptake of drugs in liposome formulations into target cells markedly impacts therapeutic efficacy. The protein corona (PC), formed by the adsorption of serum proteins onto the liposome surface, binds to specific surface receptors of target cells, influencing the uptake pathway. We investigated the uptake pathway into leukemia cells based on PC analysis of CPX-351, a liposome containing cytarabine and daunorubicin in a fixed 5:1 synergistic molar ratio. The PC of CPX-351 mixed with fetal bovine serum was analyzed by nanoflow liquid chromatography-tandem mass spectrometry. CPX-351 uptake in HL-60, K562, and THP-1 leukemia cell lines was measured by flow cytometry using daunorubicin fluorescence. The major components of CPX-351 PC include apolipoproteins A-I and A-II, which bind to scavenger receptor class B type 1 (SR-BI), a nonendocytic pathway that takes up only liposome contents. SR-BI was expressed in each cell, and its expression correlated with CPX-351 uptake. The uptake was significantly decreased by the inhibition of clathrin-mediated endocytosis and macropinocytosis. Additionally, blocks lipid transport-1 (BLT-1), a selective inhibitor of SR-BI, decreased the uptake; however, high-dose BLT-1 addition significantly increased the uptake, which was more strongly inhibited by macropinocytosis suppression compared with clathrin-mediated endocytosis. BLT-1 enhances the binding of SR-BI to liposomes in a dose-dependent manner. These findings indicate that the enhancement of binding between SR-BI and CPX-351 activates different pathways, such as macropinocytosis, distinct from CPX-351 alone. SR-BI may be a biomarker for CPX-351 therapy, and the combination of CPX-351 with high-dose BLT-1 may augment therapeutic efficacy.
Collapse
Affiliation(s)
- Hiroaki Araie
- Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Naoko Hosono
- Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
| | - Takahiro Yamauchi
- Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| |
Collapse
|
32
|
Motawea A, Maria SN, Maria DN, Jablonski MM, Ibrahim MM. Genistein transfersome-embedded topical delivery system for skin melanoma treatment: in vitro and ex vivo evaluations. Drug Deliv 2024; 31:2372277. [PMID: 38952058 PMCID: PMC11221477 DOI: 10.1080/10717544.2024.2372277] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 06/11/2024] [Indexed: 07/03/2024] Open
Abstract
Skin melanoma is considered the most dangerous form of skin cancer due to its association with high risk of metastasis, high mortality rate and high resistance to different treatment options. Genistein is a natural isoflavonoid with known chemotherapeutic activity. Unfortunately, it has low bioavailability due to its poor aqueous solubility and excessive metabolism. In the current study, genistein was incorporated into transferosomal hydrogel to improve its bioavailability. The prepared transferosomal formulations were characterized regarding: particle size; polydispersity index; zeta potential; encapsulation efficiency; TEM; FTIR; DSC; XRD; in vitro drug release; viscosity; pH; ex vivo anti-tumor activity on 3D skin melanoma spheroids and 1-year stability study at different storage temperatures. The optimized formulation has high encapsulation efficiency with an excellent particle size that will facilitate its penetration through the skin. The transfersomes have a spherical shape with sustained drug release profile. The anti-tumor activity evaluation of genistein transfersome revealed that genistein is a potent chemotherapeutic agent with enhanced penetration ability through the melanoma spheroids when incorporated into transfersomes. Stability study results demonstrate the high physical and chemical stability of our formulations. All these outcomes provide evidence that our genistein transferosomal hydrogel is a promising treatment option for skin melanoma.
Collapse
Affiliation(s)
- Amira Motawea
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Sara N. Maria
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
- Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Doaa N. Maria
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
- Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Monica M. Jablonski
- Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Mohamed Moustafa Ibrahim
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
- Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA
| |
Collapse
|
33
|
Chen J, Yao Y, Mao X, Chen Y, Ni F. Liver-targeted delivery based on prodrug: passive and active approaches. J Drug Target 2024; 32:1155-1168. [PMID: 39072411 DOI: 10.1080/1061186x.2024.2386416] [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: 03/20/2024] [Revised: 07/26/2024] [Accepted: 07/26/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND The liver, a central organ in human metabolism, is often the primary target for drugs. However, conditions such as viral hepatitis, cirrhosis, non-alcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC) present substantial health challenges worldwide. Existing treatments, which suffer from the non-specific distribution of drugs, frequently fail to achieve desired efficacy and safety, risking unnecessary liver harm and systemic side effects. PURPOSE The aim of this review is to synthesise the latest progress in the design of liver-targeted prodrugs, with a focus on passive and active targeting strategies, providing new insights into the development of liver-targeted therapeutic approaches. METHODS This study conducted an extensive literature search through databases like Google Scholar, PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI), systematically collecting and selecting recent research on liver-targeted prodrugs. The focus was on targeting mechanisms, including the Enhanced Permeability and Retention (EPR) effect, the unique microenvironment of liver cancer, and active targeting through specific transporters and receptors. RESULTS Active targeting strategies achieve precise drug delivery by binding specific ligands to liver surface receptors. Passive targeting takes advantage of the EPR effect and tumour characteristics to enrich drugs in liver tumours. The review details successful cases of using small molecule ligands, peptides, antibodies and nanoparticles as drug carriers. CONCLUSION Liver-targeted prodrug strategies show great potential in enhancing the efficacy of drug treatment and reducing side effects for liver diseases. Future research should balance the advantages and limitations of both targeting strategies, focusing on optimising drug design and targeting efficiency, especially for clinical application. In-depth research on liver-specific receptors and the development of innovative targeting molecules are crucial for advancing the field of liver-targeted prodrugs.
Collapse
Affiliation(s)
- Jiaqi Chen
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yingrui Yao
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaoran Mao
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuzhou Chen
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Feng Ni
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, China
| |
Collapse
|
34
|
Tong F, Wang Y, Xu Y, Zhou Y, He S, Du Y, Yang W, Lei T, Song Y, Gong T, Gao H. MMP-2-triggered, mitochondria-targeted PROTAC-PDT therapy of breast cancer and brain metastases inhibition. Nat Commun 2024; 15:10382. [PMID: 39613781 PMCID: PMC11607387 DOI: 10.1038/s41467-024-54854-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 11/19/2024] [Indexed: 12/01/2024] Open
Abstract
Proteolytic targeting chimera (PROTAC) technology is a protein-blocking technique and induces antitumor effects, with potential advantages. However, its effect is limited by insufficient distribution and accumulation in tumors. Herein, a transformable nanomedicine (dBET6@CFMPD) with mitochondrial targeting capacity is designed and constructed to combine PROTAC with photodynamic therapy (PDT). In this work, we demonstrate that dBET6@CFMPD exhibits great biodistribution and retention, and can induce potent antitumor response to suppress primary and metastatic tumors, becoming a nanomedicine with potential in cancer combination therapy.
Collapse
Affiliation(s)
- Fan Tong
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yufan Wang
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yanyan Xu
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yang Zhou
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570200, China
| | - Siqin He
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yufan Du
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Wenqin Yang
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Ting Lei
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yujun Song
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Tao Gong
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Huile Gao
- Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
| |
Collapse
|
35
|
Dejeu IL, Vicaș LG, Marian E, Ganea M, Frenț OD, Maghiar PB, Bodea FI, Dejeu GE. Innovative Approaches to Enhancing the Biomedical Properties of Liposomes. Pharmaceutics 2024; 16:1525. [PMID: 39771504 PMCID: PMC11728823 DOI: 10.3390/pharmaceutics16121525] [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: 10/13/2024] [Revised: 10/31/2024] [Accepted: 11/25/2024] [Indexed: 01/16/2025] Open
Abstract
Liposomes represent a promising class of drug delivery systems that enhance the therapeutic efficacy and safety of various pharmaceutical agents. Also, they offer numerous advantages compared to traditional drug delivery methods, including targeted delivery to specific sites, controlled release, and fewer side effects. This review meticulously examines the methodologies employed in the preparation and characterization of liposomal formulations. With the rising incidence of adverse drug reactions, there is a pressing need for innovative delivery strategies that prioritize selectivity, specificity, and safety. Nanomedicine promises to revolutionize diagnostics and treatments, addressing current limitations and improving disease management, including cancer, which remains a major global health challenge. This paper aims to conduct a comprehensive study on the interest of biomedical research regarding nanotechnology and its implications for further applications.
Collapse
Affiliation(s)
- Ioana Lavinia Dejeu
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 29 Nicolae Jiga Street, 410028 Oradea, Romania; (I.L.D.); (E.M.); (M.G.); (O.D.F.)
| | - Laura Grațiela Vicaș
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 29 Nicolae Jiga Street, 410028 Oradea, Romania; (I.L.D.); (E.M.); (M.G.); (O.D.F.)
| | - Eleonora Marian
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 29 Nicolae Jiga Street, 410028 Oradea, Romania; (I.L.D.); (E.M.); (M.G.); (O.D.F.)
| | - Mariana Ganea
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 29 Nicolae Jiga Street, 410028 Oradea, Romania; (I.L.D.); (E.M.); (M.G.); (O.D.F.)
| | - Olimpia Daniela Frenț
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 29 Nicolae Jiga Street, 410028 Oradea, Romania; (I.L.D.); (E.M.); (M.G.); (O.D.F.)
| | - Paula Bianca Maghiar
- Doctoral School of Biomedical Science, University of Oradea, 1 University Street, 410087 Oradea, Romania; (P.B.M.); (F.I.B.)
| | - Flaviu Ionut Bodea
- Doctoral School of Biomedical Science, University of Oradea, 1 University Street, 410087 Oradea, Romania; (P.B.M.); (F.I.B.)
| | - George Emanuiel Dejeu
- Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 10 Piata 1 Decembrie Street, 410073 Oradea, Romania;
| |
Collapse
|
36
|
Ma X, Tian Y, Yang R, Wang H, Allahou LW, Chang J, Williams G, Knowles JC, Poma A. Nanotechnology in healthcare, and its safety and environmental risks. J Nanobiotechnology 2024; 22:715. [PMID: 39548502 PMCID: PMC11566612 DOI: 10.1186/s12951-024-02901-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: 07/22/2024] [Accepted: 10/03/2024] [Indexed: 11/18/2024] Open
Abstract
Nanotechnology holds immense promise in revolutionising healthcare, offering unprecedented opportunities in diagnostics, drug delivery, cancer therapy, and combating infectious diseases. This review explores the multifaceted landscape of nanotechnology in healthcare while addressing the critical aspects of safety and environmental risks associated with its widespread application. Beginning with an introduction to the integration of nanotechnology in healthcare, we first delved into its categorisation and various materials employed, setting the stage for a comprehensive understanding of its potential. We then proceeded to elucidate the diverse healthcare applications of nanotechnology, spanning medical diagnostics, tissue engineering, targeted drug delivery, gene delivery, cancer therapy, and the development of antimicrobial agents. The discussion extended to the current situation surrounding the clinical translation and commercialisation of these cutting-edge technologies, focusing on the nanotechnology-based healthcare products that have been approved globally to date. We also discussed the safety considerations of nanomaterials, both in terms of human health and environmental impact. We presented the in vivo health risks associated with nanomaterial exposure, in relation with transport mechanisms, oxidative stress, and physical interactions. Moreover, we highlighted the environmental risks, acknowledging the potential implications on ecosystems and biodiversity. Lastly, we strived to offer insights into the current regulatory landscape governing nanotechnology in healthcare across different regions globally. By synthesising these diverse perspectives, we underscore the imperative of balancing innovation with safety and environmental stewardship, while charting a path forward for the responsible integration of nanotechnology in healthcare.
Collapse
Affiliation(s)
- Xiaohan Ma
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK.
| | - Yaxin Tian
- United InnoMed (Shanghai) Limited, F/2, E-1, No.299, Kangwei Rd, Pudong District, Shanghai, China
| | - Ren Yang
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK
| | - Haowei Wang
- Centre for Precision Healthcare, UCL Division of Medicine, University College London, London, WC1E 6JF, UK
| | - Latifa W Allahou
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Jinke Chang
- UCL Centre for Biomaterials in Surgical Reconstruction and Regeneration, Division of Surgery & Interventional Science, University College London, London, NW3 2PF, UK
| | - Gareth Williams
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Jonathan C Knowles
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Med-Icine, Dankook University, Cheonan, 31116, South Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, South Korea
| | - Alessandro Poma
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK.
| |
Collapse
|
37
|
Hefnawy A, Abdelhamid AS, Abdelaziz MM, Elzoghby AO, Khalil IA. Recent advances in nano-based drug delivery systems for treatment of liver cancer. J Pharm Sci 2024; 113:3145-3172. [PMID: 39151795 DOI: 10.1016/j.xphs.2024.08.012] [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: 04/01/2024] [Revised: 08/13/2024] [Accepted: 08/13/2024] [Indexed: 08/19/2024]
Abstract
Liver cancer is one of the aggressive primary tumors as evident by high rate of incidence and mortality. Conventional treatments (e.g. chemotherapy) suffer from various drawbacks including wide drug distribution, low localized drug concentration, and severe off-site toxicity. Therefore, they cannot satisfy the mounting need for safe and efficient cancer therapeutics, and alternative novel strategies are needed. Nano-based drug delivery systems (NDDSs) are among these novel approaches that can improve the overall therapeutic outcomes. NDDSs are designed to encapsulate drug molecules and target them specifically to liver cancer. Thus, NDDSs can selectively deliver therapeutic agents to the tumor cells and avoid distribution to off-target sites which should improve the safety profile of the active agents. Nonetheless, NDDSs should be well designed, in terms of the preparing materials, nanocarriers structure, and the targeting strategy, in order to accomplish these objectives. This review discusses the latest advances of NDDSs for cancer therapy with emphasis on the aforementioned essential design components. The review also entails the challenges associated with the clinical translation of NDDSs, and the future perspectives towards next-generation NDDSs.
Collapse
Affiliation(s)
- Amr Hefnawy
- Smyth Lab, College of Pharmacy, University of Texas at Austin, TX 78712, USA.
| | - Ahmed S Abdelhamid
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
| | - Moustafa M Abdelaziz
- Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047, USA.
| | - Ahmed O Elzoghby
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | - Islam A Khalil
- Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City 12582, Giza, Egypt.
| |
Collapse
|
38
|
Raj A, Chandran C S, Dua K, Kamath V, Alex AT. Targeting overexpressed surface proteins: A new strategy to manage the recalcitrant triple-negative breast cancer. Eur J Pharmacol 2024; 981:176914. [PMID: 39154820 DOI: 10.1016/j.ejphar.2024.176914] [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: 03/25/2024] [Revised: 08/08/2024] [Accepted: 08/15/2024] [Indexed: 08/20/2024]
Abstract
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous cancer that lacks all three molecular markers, Estrogen, Progesterone, and Human Epidermal Growth Factor Receptor 2 (HER2). This unique characteristic of TNBC makes it more resistant to hormonal therapy; hence, chemotherapy and surgery are preferred. Active targeting with nanoparticles is more effective in managing TNBC than a passive approach. The surface of TNBC cells overexpresses several cell-specific proteins, which can be explored for diagnostic and therapeutic purposes. Immunohistochemical analysis has revealed that TNBC cells overexpress αVβ3 integrin, Intercellular Adhesion Molecule 1 (ICAM-1), Glucose Transporter 5 (GLUT5), Transmembrane Glycoprotein Mucin 1 (MUC-1), and Epidermal Growth Factor Receptor (EGFR). These surface proteins can be targeted using ligands, such as aptamers, antibodies, and sugar molecules. Targeting the surface proteins of TNBC with ligands helps harmonize treatment and improve patient compliance. In this review, we discuss the proteins expressed, which are limited to αVβ3 integrin proteins, ICAM-1, GLUT-5, MUC1, and EGFR, on the surface of TNBC, the challenges associated with the preclinical setup of breast cancer for targeted nanoformulations, internalization techniques and their challenges, suggestions to overcome the limitations of successful translation of nanoparticles, and the possibility of ligand-conjugated nanoparticles targeting these surface receptors for a better therapeutic outcome.
Collapse
Affiliation(s)
- Alan Raj
- Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka state, India, 576104.
| | - Sarath Chandran C
- Department of Pharmaceutics, College of Pharmaceutical Sciences, Government Medical College Kannur, Pariyaram, Kerala, India, 670 503; Kerala University of Health Sciences, Thrissur, Kerala, India - 680 596.
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, Faculty of Health, University of Technology Sydney, Sydney, Australia-2007; Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Sydney, Australia-2007.
| | - Venkatesh Kamath
- Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka state, India, 576104.
| | - Angel Treasa Alex
- Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka state, India, 576104.
| |
Collapse
|
39
|
Song W, Zhang H, Lu Y, Zhang H, Ni J, Chang L, Gu Y, Wang G, Xu T, Wu Z, Wang K. KHSRP knockdown inhibits papillary renal cell carcinoma progression and sensitizes to gemcitabine. Front Pharmacol 2024; 15:1446920. [PMID: 39439895 PMCID: PMC11493689 DOI: 10.3389/fphar.2024.1446920] [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: 06/10/2024] [Accepted: 09/23/2024] [Indexed: 10/25/2024] Open
Abstract
Patients diagnosed with papillary renal cell carcinoma (pRCC) exhibit a high rate of clinical metastasis; however, the underlying molecular mechanism is unclear. In this study, KH-type splicing regulatory protein (KHSRP) participated in pRCC progression and was associated with metastasis. It was positively correlated with the hallmark of epithelial-mesenchymal transition. KHSRP inhibition effectively alleviated the cellular function of migration and invasion. Additionally, KHSRP knockdown inhibited the proliferative ability of pRCC cells. A pharmaceutical screening was based on the KHSRP protein structure. Gemcitabine (Gem) decreased KHSRP expression. UIO-66@Gem@si-KHSRP (UGS) nanoparticles (NPs) were prepared for targeted delivery and applied in both in vitro and in vivo experiments to explore the clinical transition of KHSRP. UGS NPs exhibited better performance in inhibiting cellular proliferation, migration, and invasion than Gem. Additionally, the in vivo experiment results confirmed their therapeutic effects in inhibiting tumor metastasis with excellent biosafety. The silico analysis indicated that KHSRP knockdown increased cytotoxic cell infiltration in the tumor microenvironment to potentiate anti-tumor effects. Thus, KHSRP can promote pRCC progression as an oncogene and serve as a target in clinical transition through UGS NP-based therapy.
Collapse
Affiliation(s)
- Wei Song
- Department of Urology, Shanghai Shidong Hospital of Yangpu District, Shanghai, China
- Department of Urology, Shanghai Putuo District People’s Hospital, Tongji University, Shanghai, China
- Department of Urology, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Heng Zhang
- Guiqian International General Hospital, Guiyang, China
| | - Yi Lu
- Department of Urology, Shanghai Shidong Hospital of Yangpu District, Shanghai, China
| | - Houliang Zhang
- Shanghai Putuo District Health Affairs Management Center, Hospital Operation Department, Shanghai, China
| | - Jinliang Ni
- Shanghai Putuo District Health Affairs Management Center, Hospital Operation Department, Shanghai, China
| | - Lan Chang
- Shanghai Putuo District Health Affairs Management Center, Hospital Operation Department, Shanghai, China
| | - Yongzhe Gu
- Department of Neurology, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Guangchun Wang
- Department of Urology, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Tianyuan Xu
- Department of Urology, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Zonglin Wu
- Department of Urology, Shanghai Shidong Hospital of Yangpu District, Shanghai, China
| | - Keyi Wang
- Department of Urology, Shanghai Shidong Hospital of Yangpu District, Shanghai, China
- Department of Urology, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| |
Collapse
|
40
|
Jiang Y, Wang C, Zu C, Rong X, Yu Q, Jiang J. Synergistic Potential of Nanomedicine in Prostate Cancer Immunotherapy: Breakthroughs and Prospects. Int J Nanomedicine 2024; 19:9459-9486. [PMID: 39371481 PMCID: PMC11456300 DOI: 10.2147/ijn.s466396] [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: 02/28/2024] [Accepted: 08/16/2024] [Indexed: 10/08/2024] Open
Abstract
Given the global prevalence of prostate cancer in men, it is crucial to explore more effective treatment strategies. Recently, immunotherapy has emerged as a promising cancer treatment due to its unique mechanism of action and potential long-term effectiveness. However, its limited efficacy in prostate cancer has prompted renewed interest in developing strategies to improve immunotherapy outcomes. Nanomedicine offers a novel perspective on cancer treatment with its unique size effects and surface properties. By employing targeted delivery, controlled release, and enhanced immunogenicity, nanoparticles can be synergized with nanomedicine platforms to amplify the effectiveness of immunotherapy in treating prostate cancer. Simultaneously, nanotechnology can address the limitations of immunotherapy and the challenges of immune escape and tumor microenvironment regulation. Additionally, the synergistic effects of combining nanomedicine with other therapies offer promising clinical outcomes. Innovative applications of nanomedicine include smart nanocarriers, stimulus-responsive systems, and precision medicine approaches to overcome translational obstacles in prostate cancer immunotherapy. This review highlights the transformative potential of nanomedicine in enhancing prostate cancer immunotherapy and emphasizes the need for interdisciplinary collaboration to drive research and clinical applications forward.
Collapse
Affiliation(s)
- Yueyao Jiang
- Department of Pharmacy, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China
| | - Chengran Wang
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China
| | - Chuancheng Zu
- China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China
| | - Xin’ao Rong
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China
| | - Qian Yu
- Department of Pharmacy, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China
| | - Jinlan Jiang
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China
| |
Collapse
|
41
|
Naguib YW, Alhaj-Suliman SO, Wafa EI, Saha S, Ebeid K, Mohammed HHH, Abdel-Rahman SA, Abuo-Rahma GEDA, Geary SM, Salem AK. Ciprofloxacin Derivative-Loaded Nanoparticles Synergize with Paclitaxel Against Type II Human Endometrial Cancer. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2302931. [PMID: 37525558 PMCID: PMC10828114 DOI: 10.1002/smll.202302931] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 07/07/2023] [Indexed: 08/02/2023]
Abstract
Combinations of chemotherapeutic agents comprise a clinically feasible approach to combat cancers that possess resistance to treatment. Type II endometrial cancer is typically associated with poor outcomes and the emergence of chemoresistance. To overcome this challenge, a combination therapy is developed comprising a novel ciprofloxacin derivative-loaded PEGylated polymeric nanoparticles (CIP2b-NPs) and paclitaxel (PTX) against human type-II endometrial cancer (Hec50co with loss of function p53). Cytotoxicity studies reveal strong synergy between CIP2b and PTX against Hec50co, and this is associated with a significant reduction in the IC50 of PTX and increased G2/M arrest. Upon formulation of CIP2b into PEGylated polymeric nanoparticles, tumor accumulation of CIP2b is significantly improved compared to its soluble counterpart; thus, enhancing the overall antitumor activity of CIP2b when co-administered with PTX. In addition, the co-delivery of CIP2b-NPs with paclitaxel results in a significant reduction in tumor progression. Histological examination of vital organs and blood chemistry was normal, confirming the absence of any apparent off-target toxicity. Thus, in a mouse model of human endometrial cancer, the combination of CIP2b-NPs and PTX exhibits superior therapeutic activity in targeting human type-II endometrial cancer.
Collapse
Affiliation(s)
- Youssef W. Naguib
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
- Department of Pharmaceutics, and Minia 61519, Egypt
| | - Suhaila O. Alhaj-Suliman
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
| | - Emad I. Wafa
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
| | - Sanjib Saha
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
| | - Kareem Ebeid
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
- Department of Pharmaceutics, and Minia 61519, Egypt
| | - Hamada H. H. Mohammed
- Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
| | - Somaya A. Abdel-Rahman
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
| | | | - Sean M. Geary
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
| | - Aliasger K. Salem
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
- Holden Comprehensive Cancer Center, University of Iowa Hospitals & Clinics, Iowa City, IA 52242, United States
| |
Collapse
|
42
|
Wang A, Walden M, Ettlinger R, Kiessling F, Gassensmith JJ, Lammers T, Wuttke S, Peña Q. Biomedical Metal-Organic Framework Materials: Perspectives and Challenges. ADVANCED FUNCTIONAL MATERIALS 2024; 34:adfm.202308589. [PMID: 39726715 PMCID: PMC7617264 DOI: 10.1002/adfm.202308589] [Citation(s) in RCA: 30] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Indexed: 12/28/2024]
Abstract
Metal-organic framework (MOF) materials are gaining significant interest in biomedical research, owing to their high porosity, crystallinity, and structural and compositional diversity. Their versatile hybrid organic/inorganic chemistry endows MOFs with the capacity to retain organic (drug) molecules, metals, and gases, to effectively channel electrons and photons, to survive harsh physiological conditions such as low pH, and even to protect sensitive biomolecules. Extensive preclinical research has been carried out with MOFs to treat several pathologies and, recently, their integration with other biomedical materials such as stents and implants has demonstrated promising performance in regenerative medicine. However, there remains a significant gap between MOF preclinical research and translation into clinically and societally relevant medicinal products. Here, we outline the intrinsic features of MOFs and discuss how these are suited to specific biomedical applications like detoxification, drug and gas delivery, or as (combination) therapy platforms. We furthermore describe relevant examples of how MOFs have been engineered and evaluated in different medical indications, including cancer, microbial, and inflammatory diseases. Finally, we critically examine the challenges facing their translation into the clinic, with the goal of establishing promising research directions and more realistic approaches that can bridge the translational gap of MOFs and MOF-containing (nano)materials.
Collapse
Affiliation(s)
- Alec Wang
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Forckenbeckstrasse 55, 52074Aachen, Germany
| | - Madeline Walden
- BCMaterials (Basque Centre for Materials, Applications & Nanostructures), Bld. Martina Casiano, 3rd. Floor UPV/EHU Science Park Barrio Sarriena s/n, 48940Leioa, Spain
| | - Romy Ettlinger
- EastChem School of Chemistry, University of St Andrews, North Haugh, St AndrewsKY16 9ST, UK
| | - Fabian Kiessling
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Forckenbeckstrasse 55, 52074Aachen, Germany
| | - Jeremiah J. Gassensmith
- Department of Chemistry and Biochemistry & Biomedical Engineering, University of Texas at Dallas, Richardson, TX75080-3021
| | - Twan Lammers
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Forckenbeckstrasse 55, 52074Aachen, Germany
| | - Stefan Wuttke
- BCMaterials (Basque Centre for Materials, Applications & Nanostructures), Bld. Martina Casiano, 3rd. Floor UPV/EHU Science Park Barrio Sarriena s/n, 48940Leioa, Spain
- IKERBASQUE, Basque Foundation for Science, 48013Bilbao, Spain
| | - Quim Peña
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Forckenbeckstrasse 55, 52074Aachen, Germany
| |
Collapse
|
43
|
Li X, Hu Y, Zhang X, Shi X, Parak WJ, Pich A. Transvascular transport of nanocarriers for tumor delivery. Nat Commun 2024; 15:8172. [PMID: 39289401 PMCID: PMC11408679 DOI: 10.1038/s41467-024-52416-0] [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: 12/05/2023] [Accepted: 09/05/2024] [Indexed: 09/19/2024] Open
Abstract
Nanocarriers (NCs) play a crucial role in delivering theranostic agents to tumors, making them a pivotal focus of research. However, the persistently low delivery efficiency of engineered NCs has been a significant challenge in the advancement of nanomedicine, stirring considerable debate. Transvascular transport is a critical pathway for NC delivery from vessels to tumors, yet a comprehensive understanding of the interactions between NCs and vascular systems remains elusive. In recent years, considerable efforts have been invested in elucidating the transvascular transport mechanisms of NCs, leading to promising advancements in tumor delivery and theranostics. In this context, we highlight various delivery mechanisms, including the enhanced permeability and retention effect, cooperative immune-driven effect, active transcytosis, and cell/bacteria-mediated delivery. Furthermore, we explore corresponding strategies aimed at enhancing transvascular transport of NCs for efficient tumor delivery. These approaches offer intriguing solutions spanning physicochemical, biological, and pharmacological domains to improve delivery and therapeutic outcomes. Additionally, we propose a forward-looking delivery framework that relies on advanced tumor/vessel models, high-throughput NC libraries, nano-bio interaction datasets, and artificial intelligence, which aims to guide the design of next-generation carriers and implementation strategies for optimized delivery.
Collapse
Affiliation(s)
- Xin Li
- DWI-Leibniz-Institute for Interactive Materials, Aachen, 52056, Germany
- Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, 52074, Germany
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China
| | - Yong Hu
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China
| | - Xingcai Zhang
- Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
| | - Xiangyang Shi
- Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China
| | - Wolfgang J Parak
- Center for Hybrid Nanostructures (CHyN), University of Hamburg, Hamburg, 20607, Germany.
| | - Andrij Pich
- DWI-Leibniz-Institute for Interactive Materials, Aachen, 52056, Germany.
- Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, 52074, Germany.
- Aachen Maastricht Institute for Biobased Materials, Maastricht University, RD Geleen, 6167, The Netherlands.
| |
Collapse
|
44
|
Solanki K, Ahmed N, Srivastava N, Meher N. Prostate-Specific Membrane Antigen-Targeted NIR Phototheranostics for Prostate Cancer. ACS APPLIED BIO MATERIALS 2024; 7:5861-5884. [PMID: 39192748 DOI: 10.1021/acsabm.4c00819] [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] [Indexed: 08/29/2024]
Abstract
The evolution of targeted cancer theranostics has revolutionized personalized medicine by integrating diagnostic and therapeutic capabilities. Prostate-specific membrane antigen (PSMA) has emerged as a key theranostic target in the context of prostate cancer, paving the way for the clinical approval of multiple drugs. However, the persistent challenge of off-target toxicity, which plagues both conventional and advanced treatment modalities such as targeted chemotherapy and radiotherapy, thus demands further innovation. Considering this critical issue, this review discusses the recent advances in the binary treatment techniques, i.e., phototherapies, that have the potential to circumvent the key concern of off-target toxicity associated with personalized chemotherapy and radiotherapy. Precisely, an up-to-date overview of the latest developments in the near-infrared (NIR)-based phototheranostic strategies for prostate cancer by targeting PSMA has been presented. Furthermore, we have discussed the associated particulars that require specific attention in enhancing the translational potential of phototheranostic techniques.
Collapse
Affiliation(s)
- Krishna Solanki
- National Institute of Pharmaceutical Education and Research, Raebareli, Lucknow, Uttar Pradesh 226002, India
| | - Nazeer Ahmed
- National Institute of Pharmaceutical Education and Research, Raebareli, Lucknow, Uttar Pradesh 226002, India
| | - Nidhi Srivastava
- National Institute of Pharmaceutical Education and Research, Raebareli, Lucknow, Uttar Pradesh 226002, India
| | - Niranjan Meher
- National Institute of Pharmaceutical Education and Research, Raebareli, Lucknow, Uttar Pradesh 226002, India
| |
Collapse
|
45
|
Longobardi G, Moore TL, Conte C, Ungaro F, Satchi‐Fainaro R, Quaglia F. Polyester nanoparticles delivering chemotherapeutics: Learning from the past and looking to the future to enhance their clinical impact in tumor therapy. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1990. [PMID: 39217459 PMCID: PMC11670051 DOI: 10.1002/wnan.1990] [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: 05/29/2024] [Revised: 07/20/2024] [Accepted: 07/23/2024] [Indexed: 09/04/2024]
Abstract
Polymeric nanoparticles (NPs), specifically those comprised of biodegradable and biocompatible polyesters, have been heralded as a game-changing drug delivery platform. In fact, poly(α-hydroxy acids) such as polylactide (PLA), poly(lactide-co-glycolide) (PLGA), and poly(ε-caprolactone) (PCL) have been heavily researched in the past three decades as the material basis of polymeric NPs for drug delivery applications. As materials, these polymers have found success in resorbable sutures, biodegradable implants, and even monolithic, biodegradable platforms for sustained release of therapeutics (e.g., proteins and small molecules) and diagnostics. Few fields have gained more attention in drug delivery through polymeric NPs than cancer therapy. However, the clinical translational of polymeric nanomedicines for treating solid tumors has not been congruent with the fervor or funding in this particular field of research. Here, we attempt to provide a comprehensive snapshot of polyester NPs in the context of chemotherapeutic delivery. This includes a preliminary exploration of the polymeric nanomedicine in the cancer research space. We examine the various processes for producing polyester NPs, including methods for surface-functionalization, and related challenges. After a detailed overview of the multiple factors involved with the delivery of NPs to solid tumors, the crosstalk between particle design and interactions with biological systems is discussed. Finally, we report state-of-the-art approaches toward effective delivery of NPs to tumors, aiming at identifying new research areas and re-evaluating the reasons why some research avenues have underdelivered. We hope our effort will contribute to a better understanding of the gap to fill and delineate the future research work needed to bring polyester-based NPs closer to clinical application. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.
Collapse
Affiliation(s)
| | - Thomas Lee Moore
- Department of PharmacyUniversity of Naples Federico IINaplesItaly
| | - Claudia Conte
- Department of PharmacyUniversity of Naples Federico IINaplesItaly
| | - Francesca Ungaro
- Department of PharmacyUniversity of Naples Federico IINaplesItaly
| | - Ronit Satchi‐Fainaro
- Department of Physiology and Pharmacology, Faculty of MedicineTel Aviv UniversityTel AvivIsrael
- Sagol School of NeurosciencesTel Aviv UniversityTel AvivIsrael
| | - Fabiana Quaglia
- Department of PharmacyUniversity of Naples Federico IINaplesItaly
| |
Collapse
|
46
|
Wang C, Zhang Y, Kong W, Rong X, Zhong Z, Jiang L, Chen S, Li C, Zhang F, Jiang J. Delivery of miRNAs Using Nanoparticles for the Treatment of Osteosarcoma. Int J Nanomedicine 2024; 19:8641-8660. [PMID: 39188861 PMCID: PMC11346496 DOI: 10.2147/ijn.s471900] [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: 04/02/2024] [Accepted: 07/31/2024] [Indexed: 08/28/2024] Open
Abstract
Osteosarcoma is the predominant primary malignant bone tumor that poses a significant global health challenge. MicroRNAs (miRNAs) that regulate gene expression are associated with osteosarcoma pathogenesis. Thus, miRNAs are potential therapeutic targets for osteosarcoma. Nanoparticles, widely used for targeted drug delivery, facilitate miRNA-based osteosarcoma treatment. Numerous studies have focused on miRNA delivery using nanoparticles to inhibit the progress of osteosarcoma. Polymer-based, lipid-based, inorganic-based nanoparticles and extracellular vesicles were used to deliver miRNAs for the treatment of osteosarcoma. They can be modified to enhance drug loading and delivery capabilities. Also, miRNA delivery was combined with traditional therapies, for example chemotherapy, to treat osteosarcoma. Consequently, miRNA delivery offers promising therapeutic avenues for osteosarcoma, providing renewed hope for patients. This review emphasizes the studies utilizing nanoparticles for miRNA delivery in osteosarcoma treatment, then introduced and summarized the nanoparticles in detail. And it also discusses the prospects for clinical applications.
Collapse
Affiliation(s)
- Chengran Wang
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| | - Yihong Zhang
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| | - Weihui Kong
- Department of Stomatology, the First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| | - Xin’ao Rong
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| | - Ziming Zhong
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| | - Lei Jiang
- Department of Geriatric Medicine, Changchun Central Hospital, Changchun, Jilin Province, People’s Republic of China
| | - Shuhan Chen
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| | - Chuang Li
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| | - Fuqiang Zhang
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| | - Jinlan Jiang
- Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China
| |
Collapse
|
47
|
Zeng Y, Gao Y, He L, Ge W, Wang X, Ma T, Xie X. Smart delivery vehicles for cancer: categories, unique roles and therapeutic strategies. NANOSCALE ADVANCES 2024; 6:4275-4308. [PMID: 39170969 PMCID: PMC11334973 DOI: 10.1039/d4na00285g] [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: 04/04/2024] [Accepted: 06/19/2024] [Indexed: 08/23/2024]
Abstract
Chemotherapy and surgery remain the primary treatment modalities for cancers; however, these techniques have drawbacks, such as cancer recurrence and toxic side effects, necessitating more efficient cancer treatment strategies. Recent advancements in research and medical technology have provided novel insights and expanded our understanding of cancer development; consequently, scholars have investigated several delivery vehicles for cancer therapy to improve the efficiency of cancer treatment and patient outcomes. Herein, we summarize several types of smart therapeutic carriers and elaborate on the mechanism underlying drug delivery. We reveal the advantages of smart therapeutic carriers for cancer treatment, focus on their effectiveness in cancer immunotherapy, and discuss the application of smart cancer therapy vehicles in combination with other emerging therapeutic strategies for cancer treatment. Finally, we summarize the bottlenecks encountered in the development of smart cancer therapeutic vehicles and suggest directions for future research. This review will promote progress in smart cancer therapy and facilitate related research.
Collapse
Affiliation(s)
- Yiyu Zeng
- Department of Stomatology, The Second Xiangya Hospital, Central South University Changsha 410011 P. R. China
| | - Yijun Gao
- Department of Stomatology, The Second Xiangya Hospital, Central South University Changsha 410011 P. R. China
| | - Liming He
- Department of Stomatology, Changsha Stomatological Hospital Changsha 410004 P. R. China
| | - Wenhui Ge
- Department of Stomatology, The Second Xiangya Hospital, Central South University Changsha 410011 P. R. China
| | - Xinying Wang
- Department of Stomatology, The Second Xiangya Hospital, Central South University Changsha 410011 P. R. China
| | - Tao Ma
- Department of Stomatology, The Second Xiangya Hospital, Central South University Changsha 410011 P. R. China
| | - Xiaoyan Xie
- Department of Stomatology, The Second Xiangya Hospital, Central South University Changsha 410011 P. R. China
| |
Collapse
|
48
|
Sui C, Wu H, Li X, Wang Y, Wei J, Yu J, Wu X. Cancer immunotherapy and its facilitation by nanomedicine. Biomark Res 2024; 12:77. [PMID: 39097732 PMCID: PMC11297660 DOI: 10.1186/s40364-024-00625-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 07/22/2024] [Indexed: 08/05/2024] Open
Abstract
Cancer immunotherapy has sparked a wave of cancer research, driven by recent successful proof-of-concept clinical trials. However, barriers are emerging during its rapid development, including broad adverse effects, a lack of reliable biomarkers, tumor relapses, and drug resistance. Integration of nanomedicine may ameliorate current cancer immunotherapy. Ultra-large surface-to-volume ratio, extremely small size, and easy modification surface of nanoparticles enable them to selectively detect cells and kill cancer cells in vivo. Exciting synergistic applications of the two approaches have emerged in treating various cancers at the intersection of cancer immunotherapy and cancer nanomedicine, indicating the potential that the combination of these two therapeutic modalities can lead to new paradigms in the treatment of cancer. This review discusses the status of current immunotherapy and explores the possible opportunities that the nanomedicine platform can make cancer immunotherapy more powerful and precise by synergizing the two approaches.
Collapse
Affiliation(s)
- Chao Sui
- Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 East Duarte, Los Angeles, CA, 91010, USA
| | - Heqing Wu
- The First Affiliated Hospital of Soochow University, Suzhou, China
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, China
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Xinxin Li
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an Shaanxi, 710072, China
| | - Yuhang Wang
- The First Affiliated Hospital of Soochow University, Suzhou, China
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, China
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Jiaqi Wei
- The First Affiliated Hospital of Soochow University, Suzhou, China
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, China
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Jianhua Yu
- Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 East Duarte, Los Angeles, CA, 91010, USA.
- Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
| | - Xiaojin Wu
- The First Affiliated Hospital of Soochow University, Suzhou, China.
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, China.
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
| |
Collapse
|
49
|
Khan MQ, Alvi MA, Nawaz HH, Umar M. Cancer Treatment Using Nanofibers: A Review. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:1305. [PMID: 39120410 PMCID: PMC11314412 DOI: 10.3390/nano14151305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/22/2024] [Accepted: 08/01/2024] [Indexed: 08/10/2024]
Abstract
Currently, the number of patients with cancer is expanding consistently because of a low quality of life. For this reason, the therapies used to treat cancer have received a lot of consideration from specialists. Numerous anticancer medications have been utilized to treat patients with cancer. However, the immediate utilization of anticancer medicines leads to unpleasant side effects for patients and there are many restrictions to applying these treatments. A number of polymers like cellulose, chitosan, Polyvinyl Alcohol (PVA), Polyacrylonitrile (PAN), peptides and Poly (hydroxy alkanoate) have good properties for the treatment of cancer, but the nanofibers-based target and controlled drug delivery system produced by the co-axial electrospinning technique have extraordinary properties like favorable mechanical characteristics, an excellent release profile, a high surface area, and a high sponginess and are harmless, bio-renewable, biofriendly, highly degradable, and can be produced very conveniently on an industrial scale. Thus, nanofibers produced through coaxial electrospinning can be designed to target specific cancer cells or tissues. By modifying the composition and properties of the nanofibers, researchers can control the release kinetics of the therapeutic agent and enhance its accumulation at the tumor site while minimizing systemic toxicity. The core-shell structure of coaxial electrospun nanofibers allows for a controlled and sustained release of therapeutic agents over time. This controlled release profile can improve the efficacy of cancer treatment by maintaining therapeutic drug concentrations within the tumor microenvironment for an extended period.
Collapse
Affiliation(s)
- Muhammad Qamar Khan
- Department of Textile Engineering, School of Engineering and Technology, National Textile University, Faisalabad 37610, Pakistan
| | - Muhammad Abbas Alvi
- Department of Textile Engineering, School of Engineering and Technology, National Textile University, Faisalabad 37610, Pakistan
| | - Hafiza Hifza Nawaz
- Department of Materials, The University of Manchester, Manchester M13 9PL, UK;
| | - Muhammad Umar
- Department of Materials, The University of Manchester, Manchester M13 9PL, UK;
| |
Collapse
|
50
|
Torres-Herrero B, Armenia I, Ortiz C, de la Fuente JM, Betancor L, Grazú V. Opportunities for nanomaterials in enzyme therapy. J Control Release 2024; 372:619-647. [PMID: 38909702 DOI: 10.1016/j.jconrel.2024.06.035] [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: 03/10/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/25/2024]
Abstract
In recent years, enzyme therapy strategies have rapidly evolved to catalyze essential biochemical reactions with therapeutic potential. These approaches hold particular promise in addressing rare genetic disorders, cancer treatment, neurodegenerative conditions, wound healing, inflammation management, and infectious disease control, among others. There are several primary reasons for the utilization of enzymes as therapeutics: their substrate specificity, their biological compatibility, and their ability to generate a high number of product molecules per enzyme unit. These features have encouraged their application in enzyme replacement therapy where the enzyme serves as the therapeutic agent to rectify abnormal metabolic and physiological processes, enzyme prodrug therapy where the enzyme initiates a clinical effect by activating prodrugs, and enzyme dynamic or starving therapy where the enzyme acts upon host substrate molecules. Currently, there are >20 commercialized products based on therapeutic enzymes, but approval rates are considerably lower than other biologicals. This has stimulated nanobiotechnology in the last years to develop nanoparticle-based solutions that integrate therapeutic enzymes. This approach aims to enhance stability, prevent rapid clearance, reduce immunogenicity, and even enable spatio-temporal activation of the therapeutic catalyst. This comprehensive review delves into emerging trends in the application of therapeutic enzymes, with a particular emphasis on the synergistic opportunities presented by incorporating enzymes into nanomaterials. Such integration holds the promise of enhancing existing therapies or even paving the way for innovative nanotherapeutic approaches.
Collapse
Affiliation(s)
- Beatriz Torres-Herrero
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC/Universidad de Zaragoza, c/ Edificio I+D, Mariano Esquillor Gómez, 50018 Zaragoza, Spain
| | - Ilaria Armenia
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC/Universidad de Zaragoza, c/ Edificio I+D, Mariano Esquillor Gómez, 50018 Zaragoza, Spain
| | - Cecilia Ortiz
- Laboratorio de Biotecnología, Facultad de Ingeniería, Universidad ORT Uruguay, Mercedes 1237, 11100 Montevideo, Uruguay
| | - Jesús Martinez de la Fuente
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC/Universidad de Zaragoza, c/ Edificio I+D, Mariano Esquillor Gómez, 50018 Zaragoza, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Avenida Monforte de Lemos, 3-5, 28029 Madrid, Spain
| | - Lorena Betancor
- Laboratorio de Biotecnología, Facultad de Ingeniería, Universidad ORT Uruguay, Mercedes 1237, 11100 Montevideo, Uruguay
| | - Valeria Grazú
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC/Universidad de Zaragoza, c/ Edificio I+D, Mariano Esquillor Gómez, 50018 Zaragoza, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Avenida Monforte de Lemos, 3-5, 28029 Madrid, Spain.
| |
Collapse
|