1
|
Bayrak E, Bayir E, Baysoy E, Özcan A, Ayan B, Saygili E, Kaleli-Can G. Nintedanib loaded iron (III) chelated melanin nanoparticles as an MRI-visible antifibrotic drug delivery system. Colloids Surf B Biointerfaces 2025; 252:114652. [PMID: 40184721 DOI: 10.1016/j.colsurfb.2025.114652] [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: 01/03/2025] [Revised: 02/20/2025] [Accepted: 03/20/2025] [Indexed: 04/07/2025]
Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal, progressive lung disease characterized by extensive scarring and thickening of lung tissue that leads to respiratory failure. Early and accurate diagnosis is crucial for monitoring disease progression and assessing therapeutic efficacy. While imaging modalities such as radiological X-rays and high-resolution computed tomography (HRCT) are commonly employed, magnetic resonance imaging (MRI) offers significant advantages, including superior soft tissue contrast and the absence of ionizing radiation. However, in lung MRIs are hindered by short transverse relaxation times, low proton density, and motion artifacts which is addressed herein by developing theranostic platform combining MRI imaging with targeted drug delivery using melanin nanoparticles conjugated with nintedanib (MNP-NIN). Chelation with ferric ions (MNP-NIN-Fe³⁺) enhanced MRI visibility enabling non-invasive imaging and drug tracking. MNP-NIN and MNP-NIN-Fe³ ⁺ nanoparticles were built with mean diameters of 189 ± 44 nm and 182 ± 35 nm, respectively and demonstrating successful NIN conjugation. Controlled NIN release followed zero-order kinetics over 36 days. MNP conjugation reduced cytotoxicity in BEAS-2B and A549 cells improving the drug's safety. MRI experiments conducted with a 7.0 T animal scanner demonstrated enhanced imaging contrast with MNP-NIN-Fe solutions compared to saline underscoring their potential for localized visualization and tracking within lung tissues. By integrating MRI diagnostics and targeted drug delivery, the MNP-NIN-Fe³ ⁺ system offers a promising solution to overcome current challenges in IPF management. This theranostic platform addresses the limitations of conventional imaging techniques while providing an innovative strategy for reducing drug-related systemic side effects and improving therapeutic efficacy.
Collapse
Affiliation(s)
- Emirhan Bayrak
- Department of Biomedical Engineering, İzmir Democracy University, İzmir 35140, Türkiye
| | - Ece Bayir
- Central Research Testing and Analysis Laboratory Research and Application Center, Ege University, Izmir 35100, Türkiye
| | - Engin Baysoy
- Department of Biomedical Engineering, Bahçeşehir University, İstanbul 34353, Türkiye; Center for Targeted Therapy Technologies (CT3), Boğaziçi University, Kandilli Campus, Çengelköy, İstanbul 34685, Türkiye
| | - Alpay Özcan
- Center for Targeted Therapy Technologies (CT3), Boğaziçi University, Kandilli Campus, Çengelköy, İstanbul 34685, Türkiye; Department of Electrical and Electronics Engineering, Boğaziçi University, İstanbul 34342, Türkiye; Systems Science and Mathematics Laboratory, Boğaziçi University, İstanbul 34342, Türkiye; Magnetic Medical Devices Laboratory, Boğaziçi University, İstanbul 34342, Türkiye
| | - Bugra Ayan
- Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
| | - Ecem Saygili
- Department of Biomedical Engineering, İzmir Democracy University, İzmir 35140, Türkiye.
| | - Gizem Kaleli-Can
- Department of Biomedical Engineering, İzmir Democracy University, İzmir 35140, Türkiye.
| |
Collapse
|
2
|
Park KH, Huh Y, Chung HJ, Konishi H, Jung J, Jeong NY. Peripheral neuroprotective potential and toxicological profile of fascaplysin in zebrafish models. Anat Cell Biol 2025; 58:274-283. [PMID: 39978927 PMCID: PMC12178704 DOI: 10.5115/acb.24.290] [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: 11/04/2024] [Revised: 11/19/2024] [Accepted: 12/18/2024] [Indexed: 02/22/2025] Open
Abstract
Fascaplysin is a bioactive compound derived from marine sponges, which have anticancer properties and potential neuroprotective effects mediated by mitigation of oxidative stress-induced neurotoxicity. This study investigated the concentration-dependent effects of fascaplysin in zebrafish models, focusing on embryonic survival, cardiac function, melanocyte formation, and peripheral nerve health. Zebrafish embryos were exposed to fascaplysin at concentrations ranging from 10 nM to 100 μM, and developmental parameters were assessed. At higher concentrations (≥1 μM), fascaplysin significantly decreased embryo survival rates, delayed hatching, impaired cardiac function, and caused morphological abnormalities, including disruption of melanocyte formation and structural deformities. By contrast, lower concentrations (10 nM and 100 nM) did not exhibit significant toxicity. In adult zebrafish, fascaplysin at 100 nM reduced the expression of superoxide-producing enzymes and preserved peripheral nerve integrity following injury, as demonstrated by maintenance of fluorescence in transgenic zebrafish with expression of green fluorescent protein in Schwann cells. These findings suggest that fascaplysin exhibits peripheral neuroprotective effects at low concentrations, potentially through the reduction of oxidative stress and preservation of Schwann cell function. However, the toxicity observed at higher concentrations highlights the importance of dose optimization. Fascaplysin is a promising candidate for the development of new therapeutic strategies for peripheral neuropathies, and further studies are required to elucidate the underlying mechanisms and validate its efficacy in mammalian models.
Collapse
Affiliation(s)
- Ki-Hoon Park
- Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul, Korea
- Department of Anesthesiology and Pain Medicine, College of Medicine, Kosin University, Busan, Korea
| | - Youngbuhm Huh
- Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul, Korea
- Department of Biomedical Science, Graduation School, Kyung Hee University, Seoul, Korea
- Department of Precision Medicine, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Hyung-Joo Chung
- Department of Anesthesiology and Pain Medicine, College of Medicine, Kosin University, Busan, Korea
| | - Hiroyuki Konishi
- Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan
- Department of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of Medicine, Nagoya, Japan
| | - Junyang Jung
- Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul, Korea
- Department of Biomedical Science, Graduation School, Kyung Hee University, Seoul, Korea
- Department of Precision Medicine, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Na Young Jeong
- Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan, Korea
| |
Collapse
|
3
|
Setia A, Mehata AK, Rengan AK, Muthu MS. Self-assembled redox sensitive mixed micelles of paclitaxel: Evaluation on 3D tumor spheroids, lung biodistribution, pharmacokinetics, optical and ultrasound/photoacoustic imaging for lung cancer therapy. Int J Pharm 2025; 681:125872. [PMID: 40553927 DOI: 10.1016/j.ijpharm.2025.125872] [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: 04/26/2025] [Revised: 06/05/2025] [Accepted: 06/17/2025] [Indexed: 06/28/2025]
Abstract
The present research aims to develop cetuximab-conjugated paclitaxel-loaded redox-sensitive TPGS/HSPC mixed micelles for EGFR-targeted lung cancer treatment. The dialysis bag diffusion method was utilized to formulate the mixed micelles. Further, various physicochemical characterization parameters have been performed. The surface charge and particle size were determined to be between -16 mV to -27 mV and 162.4 to 239.8 nm, respectively. In vitro drug release for targeted mixed micelles at pH 5.5 with 20 mM GSH was found to be 86 % after 24 h. The 3D A549 tumor spheroid penetration revealed that the uptake of targeted mixed micelles was found to be higher. Moreover, the 3D A549 tumor spheroid growth inhibition found that the targeted mixed micelles showed ∼74 % inhibition after seven days of treatment. Further, the live/dead assay revealed that the targeted mixed micelles show higher dead cells compared to the pure drug. Also, the cytotoxicity investigation revealed that the activity of targeted mixed micelles was 6.22-fold higher compared to the pure drug. The in vivo lung biodistribution and pharmacokinetic studies showed promising results. In addition, targeting efficiency was further evaluated using imaging modalities such as IVIS and ultrasound/photoacoustic in a benzo(a)pyrene-induced lung cancer mice model.
Collapse
Affiliation(s)
- Aseem Setia
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (IIT) BHU, Varanasi 221005 UP, India
| | - Abhishesh Kumar Mehata
- Department of Biomedical Engineering, Indian Institute of Technology (IIT), Hyderabad, India
| | - Aravind Kumar Rengan
- Department of Biomedical Engineering, Indian Institute of Technology (IIT), Hyderabad, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (IIT) BHU, Varanasi 221005 UP, India.
| |
Collapse
|
4
|
Nagaraj K. State-of-the-art surfactant-based coatings for biomaterials: Innovations, applications, and future prospects in biomedical engineering. Int J Pharm 2025:125879. [PMID: 40541624 DOI: 10.1016/j.ijpharm.2025.125879] [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: 03/20/2025] [Revised: 06/16/2025] [Accepted: 06/17/2025] [Indexed: 06/22/2025]
Abstract
Surfactants play a vital role in modifying the surface properties of biomaterials, enhancing their functionality in medical applications such as implants, drug delivery systems, and tissue engineering. This review examines surfactant-based coatings, focusing on their classification, adsorption mechanisms, and impact on biomaterial performance. Various surfactant types (ionic, nonionic, and amphoteric) and coating techniques, including dip-coating, spin-coating, layer-by-layer self-assembly, plasma polymerization, and Langmuir-Blodgett methods, are analysed. Surfactant coatings are critical in four major biomedical areas: preventing biofilm formation on implants with antimicrobial agents (e.g., silver-surfactant composites, quaternary ammonium surfactants); improving biocompatibility and hemocompatibility in devices such as cardiovascular stents; controlled drug delivery by micelle-based delivery systems; and smart, stimulus-responsive surfaces that respond to pH or temperature changes. Although surfactant-assisted coatings demonstrate significant potential in improving biomaterial properties, challenges such as stability, cytotoxicity, and scalability hinder their widespread adoption. Advancements in green surfactants, nanotechnology, and computational modeling offer promising solutions to these limitations. Future research should prioritize biodegradable surfactants, nanoscale modifications, and predictive modeling to optimize surfactant-biomaterial interactions for enhanced biomedical applications.
Collapse
Affiliation(s)
- Karuppiah Nagaraj
- Center for Global Health Research (CGHR), Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha Nagar, Thandalam, Kanchipuram - Chennai Rd, Chennai 602105 Tamil Nadu, India.
| |
Collapse
|
5
|
Pandey S, Joshi S, Tripathi P, Gupta A, Yadav JS. A review on targeting tunable nanocarrier interaction, physiochemical properties, and futuristic nanocarrier. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167956. [PMID: 40541801 DOI: 10.1016/j.bbadis.2025.167956] [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: 02/22/2025] [Revised: 05/11/2025] [Accepted: 06/16/2025] [Indexed: 06/22/2025]
Abstract
Targeting nanotechnology has emerged as a promising approach in drug delivery systems, offering enhanced therapeutic efficacy and reduced side effects. The physicochemical properties of nanocarriers largely influence the interaction of the nanocarrier within the body and its intended targets. Factors such as size, shape, surface charge, and elasticity play crucial roles in determining the nanocarrier's ability to navigate biological barriers, evade the immune system, and selectively accumulate at the target site. Recent advancements in nanotechnology have led to the development of newer nanocarriers with improved targeting capabilities. These innovative designs incorporate smart materials that respond to specific stimuli, such as pH changes or enzyme activity, allowing precise control over drug release. The understanding and optimization of these physicochemical properties are essential for designing more effective and efficient targeted drug delivery systems, potentially revolutionizing the treatment of various diseases, particularly in cancer therapy. Additionally, surface modifications with ligands further enhance the specificity of nanocarrier-target interactions. The intersection of protein corona, tumor microenvironment, biological barriers, and nanoparticles' physicochemical properties offers several challenges in cancer-targeted treatment. Moreover, we discussed the current situation and remaining challenges of various targeting methods with receptors, nanocarrier systems targeting carcinoma, which could facilitate the advancement of targeted nanodrug delivery systems in the future. This review synthesizes advances in nanocarriers design from 2015 to 2025, focusing on cancer-specific targeting, offering a thorough analysis of all critical parameters that need to be meticulously studied to select the most suitable nanocarrier approaches for successful clinical translation.
Collapse
Affiliation(s)
- Sonia Pandey
- Department of Pharmacy, Yashraj College of Professional Studies, Kanpur, U.P. 209217, India.
| | - Shrikant Joshi
- Maliba Pharmacy College, UkaTarsadia University, Bardoli, Gujarat 394350, India
| | - Purnima Tripathi
- Anangpuria School of Pharmaceutical Sciences, Ballabgarh, Faridabad 121004, Haryana, India
| | - Arti Gupta
- Shri Ram Murti Smarak Barelly, CET (Pharmacy), 209859, India
| | | |
Collapse
|
6
|
Ganpisetti R, Giridharan S, Vaskuri GSSJ, Narang N, Basim P, Dokmeci MR, Ermis M, Rojekar S, Gholap AD, Kommineni N. Biological Nanocarriers in Cancer Therapy: Cutting Edge Innovations in Precision Drug Delivery. Biomolecules 2025; 15:802. [PMID: 40563442 DOI: 10.3390/biom15060802] [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: 05/01/2025] [Revised: 05/24/2025] [Accepted: 05/29/2025] [Indexed: 06/28/2025] Open
Abstract
Cancer is a highly detrimental and fatal illness that poses a significant threat to human well-being. The pattern of cancer treatment is continuously being optimized by the advancement of old treatment approaches and the invention of novel treatment modes. Nanotechnology-based approaches are emerging as powerful candidates in the development of these advanced methods for treating tumors. This article provides a concise overview of nanotechnology for cancer or cancer nanomedicine and its applications. In light of prevalent issues, such as inadequate precision in targeting initial chemotherapy drugs, susceptibility of nucleic acid drugs to degradation, gene delivery, and the occurrence of common immune-related adverse events during immunotherapy, we explore the potential integration of nanomedicine with these treatment approaches and illustrative examples and highlight the benefits that arise from the utilization of nanomedicine.
Collapse
Affiliation(s)
- Ramesh Ganpisetti
- Terasaki Institute of Biomedical Sciences, 21100 Erwin St, Woodland Hills, Los Angeles, CA 91367-3712, USA
| | - Sanjay Giridharan
- Arizona State University, 1151 S. Forest AV Tempe, Tempe, AZ 85281, USA
| | - G S Sainaga Jyothi Vaskuri
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center (UTHSC), Memphis, TN 38163, USA
| | - Nikesh Narang
- Department of Ophthalmology and Visual Sciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
| | - Pratap Basim
- Thermo Fisher Scientific Inc., Cincinnati, OH 45237, USA
| | - Mehmet Remzi Dokmeci
- Terasaki Institute of Biomedical Sciences, 21100 Erwin St, Woodland Hills, Los Angeles, CA 91367-3712, USA
| | - Menekse Ermis
- Terasaki Institute of Biomedical Sciences, 21100 Erwin St, Woodland Hills, Los Angeles, CA 91367-3712, USA
| | - Satish Rojekar
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Amol D Gholap
- Department of Pharmaceutics, St. John Institute of Pharmacy and Research, Palghar 401404, Maharashtra, India
| | | |
Collapse
|
7
|
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
|
8
|
Zhang N, Jing Z, Song J, Liang Q, Xu Y, Xu Z, Wen L, Wei P. Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers. Biomolecules 2025; 15:763. [PMID: 40563405 DOI: 10.3390/biom15060763] [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: 03/21/2025] [Revised: 05/14/2025] [Accepted: 05/23/2025] [Indexed: 06/28/2025] Open
Abstract
Mutations in the p53 gene are frequently observed in various cancers, prompting the initiation of efforts to restore p53 function as a therapeutic approach several decades ago. Nevertheless, only a limited number of drug development initiatives have progressed to late-stage clinical trials, and to date, no p53-targeted therapies have received approval in the USA or Europe. This situation can be attributed primarily to the characteristics of p53 as a nuclear transcription factor, which lacks the conventional features associated with drug targets and has historically been considered "undruggable". In recent years, however, several promising strategies have emerged, including the enhanced iterations of previous approaches and novel techniques aimed at targeting proteins that have traditionally been considered undruggable. There is a growing interest in small molecules that can restore the tumor-suppressive functions of mutant p53 proteins, and the development of drugs specifically designed for particular p53 mutation types is currently underway. Other approaches aim to deplete mutant p53 or exploit vulnerabilities associated with its expression. Additionally, genetic therapy strategy and approaches have rekindled interest. Advances in mutant p53 biology, compound mechanisms, treatment modalities, and nanotechnology have opened up new avenues for p53-based therapies. However, significant challenges remain in clinical development. This review reassesses the progress in targeting p53-mutant cancers, discusses the obstacles in translating these approaches into effective therapies, and highlights p53-based therapies via nanotechnology.
Collapse
Affiliation(s)
- Na Zhang
- Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Zhiyuan Jing
- Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Jie Song
- Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Qiyue Liang
- Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Yuxue Xu
- Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Zhaowei Xu
- Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Longping Wen
- Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
| | - Pengfei Wei
- Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| |
Collapse
|
9
|
Wen X, Hao Y. The combined application of exosomes/exosome-based drug preparations and ultrasound. J Mater Chem B 2025. [PMID: 40390561 DOI: 10.1039/d4tb01530d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2025]
Abstract
Exosomes are small extracellular vesicles with a diameter of 30-150 nm, secreted by a variety of cells and containing various active substances such as nucleic acids, proteins and lipids. The use of exosomes as drug carriers for targeted delivery of therapeutics has been studied for a long time. Ultrasound is recognized as a non-invasive diagnostic and therapeutic method for assisting drug loading and targeted delivery, cellular uptake and therapy. In this review, we summarize the applications of ultrasound in assisting drug loading into exosomes, targeted delivery of exosome-based drug formulations, cellular uptake, and therapy, and explore the prospects for the combined application of exosomes/exosome-based drug formulations and ultrasound.
Collapse
Affiliation(s)
- Xiuli Wen
- Department of Ultrasound, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, P. R. China.
| | - Yi Hao
- Department of Ultrasound, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, P. R. China.
| |
Collapse
|
10
|
Sahane P, Puri N, Khairnar P, Phatale V, Shukla S, Priyadarshinee A, Srivastava S. Harnessing Folate Receptors: A Comprehensive Review on the Applications of Folate-Adorned Nanocarriers for the Management of Melanoma. ACS APPLIED BIO MATERIALS 2025; 8:3623-3656. [PMID: 40275606 DOI: 10.1021/acsabm.5c00077] [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: 04/26/2025]
Abstract
The advancement in exclusively tailored therapeutic delivery systems has escalated a great deal of interest in targeted delivery to augment therapeutic efficacy and to lessen adverse effects. The targeted delivery approach promisingly helps to surmount the unmet clinical needs of conventional therapies, including chemoresistance, limited penetration, and side effects. In the case of melanoma, various receptors were overexpressed on the tumor site, among which folate receptor (FR) targeting is considered to be a progressive approach for managing melanoma. FRs are the macromolecules of the glycosyl phosphatidylinositol-attached protein that possess globular assembly with a greater affinity toward specific ligands. So, the functional ligands can be utilized to design targeted nanocarriers (NCs) that can effectively bind to overexpressed FRs. Hence, folate-adorned NCs (FNCs) offer various benefits such as site-specific targeting, cargo protection, and minimizing toxicity. This review focuses on the insights and implications of FRs, targeting FRs, and mechanisms, challenges, and advantages of FNCs. Further, the applications of various FNCs, such as liposomes, polymeric NCs, albumin nanoparticles, inorganic NCs, liquid crystalline nanoparticles, and nanogels, have been elaborated for melanoma therapy. Likewise, the potential of FNCs in immunotherapy, photodynamic therapy, chemotherapy, gene therapy, photothermal therapy, and tumor imaging has been exhaustively discussed. Furthermore, translational hurdles and potential solutions are discussed in detail. The present review is expected to give thoughtful ideas to researchers, industry stakeholders, and formulation scientists for the efficacious development of FNCs.
Collapse
Affiliation(s)
- Prajakta Sahane
- Pharmaceutical Innovation and Translational Research Lab (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India
| | - Niharika Puri
- Pharmaceutical Innovation and Translational Research Lab (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India
| | - Pooja Khairnar
- Pharmaceutical Innovation and Translational Research Lab (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India
| | - Vivek Phatale
- Pharmaceutical Innovation and Translational Research Lab (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India
| | - Shalini Shukla
- Pharmaceutical Innovation and Translational Research Lab (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India
| | - Abhipsa Priyadarshinee
- Pharmaceutical Innovation and Translational Research Lab (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India
| | - Saurabh Srivastava
- Pharmaceutical Innovation and Translational Research Lab (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India
| |
Collapse
|
11
|
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
|
12
|
Dirheimer L, Cortese S, Dolivet G, Merlin JL, Marchal F, Mastronicola R, Bezdetnaya L. Fluorescence Imaging-Assessed Surgical Margin Detection in Head and Neck Oncology by Passive and Active Targeting. Mol Diagn Ther 2025:10.1007/s40291-025-00781-x. [PMID: 40342044 DOI: 10.1007/s40291-025-00781-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2025] [Indexed: 05/11/2025]
Abstract
Surgery remains the gold standard in the management of head and neck squamous cell carcinoma (HNSCC). However, the anatomical complexity of these cancers, combined with the difficulty in discriminating between healthy and cancerous tissue and the detection of microlesions, complicates tumor resection, resulting in positive surgical margins, which are associated with a poor patient prognosis. Fluorescence-guided surgery (FGS) has emerged as a promising technique in the management of HNSCC, improving tumor resection and margin assessment. FGS strategies can be roughly divided into three approaches; namely, natural tissue autofluorescence, passive delivery of fluorescent contrast agents, and active targeting. This review provides a comprehensive overview of the advances made in FGS of head and neck cancers, particularly aiming to improve surgical margin assessment. Recently, the field has shown promising results by addressing contrast agents targeted to the overexpressed epidermal growth factor receptor (EGFR), both in preclinical and clinical settings. The identification of new targets such as αVβ6 integrin, uPAR, PARP1, and so on, as well as the development of contrast agents, are key steps in the further development of FGS of head and neck cancers, making it an essential tool in precision oncology. Among these, as was demonstrated in preclinical studies, the αVβ6 integrin is emerging as a promising target due to its high and specific expression in tumor and tumor margins.
Collapse
Affiliation(s)
- L Dirheimer
- Research Department, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy, France
| | - S Cortese
- Surgical Department, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy, France
| | - G Dolivet
- Surgical Department, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy, France
- Université de Lorraine, CNRS, CRAN, 54000, Nancy, France
| | - J L Merlin
- Université de Lorraine, CNRS, CRAN, 54000, Nancy, France
- Département de Biopathologie, Institut de Cancérologie de Lorraine, CNRS UMR 7039 CRAN-Université de Lorraine, 6 avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy Cedex, France
| | - F Marchal
- Surgical Department, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy, France
- Université de Lorraine, CNRS, CRAN, 54000, Nancy, France
| | - R Mastronicola
- Surgical Department, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy, France
- Université de Lorraine, CNRS, CRAN, 54000, Nancy, France
| | - L Bezdetnaya
- Research Department, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy, France.
- Université de Lorraine, CNRS, CRAN, 54000, Nancy, France.
| |
Collapse
|
13
|
Yang JW, Yoon T, Kim H, Joo KI, Cha HJ. Acrylated Bioengineered Mussel Protein-Based Adhesive Nanoparticles for Locoregional and Sustained Drug Delivery. ACS Biomater Sci Eng 2025. [PMID: 40335274 DOI: 10.1021/acsbiomaterials.5c00390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/09/2025]
Abstract
Nanoparticles have emerged as promising drug carriers owing to their ability to permeate cell membranes and enhance drug stability. However, their clinical application faces significant challenges, including rapid diffusion, inefficient retention at target sites, and burst drug release. This study proposes the use of adhesive nanoparticles derived from acrylated bioengineered mussel adhesive proteins (MAPs). Acrylic groups were conjugated to lysine residues in MAPs to form polyacrylate-MAPs by photo-cross-linking, retaining sufficient 3,4-dihydroxyphenylalanine residues for strong tissue adhesion in aqueous environments. These nanoparticles were designed to adhere effectively to the administration sites and facilitate continuous drug release. In vitro and in vivo evaluations demonstrated that the acrylated MAP-based nanoparticles exhibited superior wet adhesive properties, sustained drug release, and long-term retention at the administration site and effectively suppressed tumor growth, ensuring that a single dose maintained a therapeutic concentration at the target site over extended periods. Thus, this approach could address the challenges of drug localization and retention, significantly improving therapeutic efficacy. This study emphasizes the versatility of bioengineered MAP-based adhesive nanoparticles for locoregional and sustained drug delivery, with promising applications in cancer therapy, regenerative medicine, and other biomedical fields.
Collapse
Affiliation(s)
- Jang Woo Yang
- Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| | - Taehee Yoon
- Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| | - Haram Kim
- Division of Chemical Engineering and Materials Science, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Kye Il Joo
- Division of Chemical Engineering and Materials Science, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Hyung Joon Cha
- Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
- Medical Science and Engineering, School of Convergence Science and Technology, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| |
Collapse
|
14
|
Nagaraj K. Surfactant-based drug delivery systems for cancer therapy: Advances, challenges, and future perspectives. Int J Pharm 2025; 679:125655. [PMID: 40320019 DOI: 10.1016/j.ijpharm.2025.125655] [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: 02/28/2025] [Revised: 04/15/2025] [Accepted: 04/27/2025] [Indexed: 05/07/2025]
Abstract
Cancer is one of the most formidable global health challenges, needing ongoing progress in therapeutic approaches. Conventional cancer treatments, such as chemotherapy, frequently suffer from low solubility, systemic toxicity, and a lack of tailored drug delivery, resulting in unwanted side effects and limited efficacy. Surfactant-based drug delivery systems have emerged as a viable method for increasing drug solubility, stability, and tailored transport to tumor locations. Surfactants, due to their amphiphilic character, play an important role in the development of various drug delivery systems, such as micelles, liposomes, nanoemulsions, and lipid-based nanoparticles, which improve drug bioavailability and therapeutic index. This article looks at the fundamental role of surfactants in drug administration, including their classification (ionic, nonionic, amphoteric, and zwitterionic) and self-assembly behavior in the formation of micellar, vesicular, and emulsified nanocarriers. Various surfactant-based drug delivery platforms in oncology are explored, including polymeric and surfactant-stabilized micelles, liposomes (e.g., Doxil), nanoemulsions, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). Furthermore, the use of surfactant-metal complexes in cancer therapy is emphasized because of their potential to improve therapeutic activity and selectivity. The review also looks at surfactant-enhanced drug targeting strategies, such as passive targeting using the enhanced permeability and retention (EPR) effect, active targeting with ligand-functionalized surfactant-based carriers, and stimuli-responsive systems designed for controlled drug release in the tumor microenvironment. Surfactant-based drug delivery advancements are explored, with an emphasis on current advances such as biodegradable and bio-inspired surfactants, combination therapies using surfactant-stabilized carriers, and AI-driven drug formulation techniques. Despite its potential, surfactant-based drug delivery systems confront several hurdles, including biocompatibility concerns, synthetic surfactant toxicity, stability issues, and scaling restrictions in pharmaceutical manufacture. Furthermore, regulatory barriers in clinical translation remain severe. Addressing these problems with innovative surfactant formulations, green chemical techniques, and sophisticated nanotechnological alterations will be critical to optimizing these systems for clinical use. This review provides a comprehensive analysis of the progress, challenges, and future perspectives of surfactant-based drug delivery systems in cancer therapy, highlighting their potential to revolutionize oncology treatments by improving drug efficacy, reducing systemic toxicity, and enabling precision medicine.
Collapse
Affiliation(s)
- Karuppiah Nagaraj
- Department of General Medicine, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha Nagar, Thandalam, Kanchipuram - Chennai Rd, Chennai 602105 Tamil Nadu, India.
| |
Collapse
|
15
|
Bakir M, Dawalibi A, Mufti MA, Behiery A, Mohammad KS. Nano-Drug Delivery Systems for Bone Metastases: Targeting the Tumor-Bone Microenvironment. Pharmaceutics 2025; 17:603. [PMID: 40430894 PMCID: PMC12115183 DOI: 10.3390/pharmaceutics17050603] [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: 04/02/2025] [Revised: 04/27/2025] [Accepted: 04/30/2025] [Indexed: 05/29/2025] Open
Abstract
Bone metastases are a prevalent and debilitating consequence of various cancers, including breast and prostate carcinomas, which significantly compromise patient quality of life due to pain, fractures, and other skeletal-related events (SREs). This review examines the pathophysiology of bone metastases, emphasizing the role of the bone microenvironment in tumor progression through mechanisms such as osteotropism and the dysregulated bone remodeling cycle. The primary focus is on the emerging nano-drug delivery systems (DDS) designed to target the bone microenvironment and improve the therapeutic index of anticancer agents. Current treatments, mainly comprising bisphosphonates and radiotherapy, provide palliative benefits but often have limited efficacy and significant side effects. Innovative strategies, such as bisphosphonate-conjugated nanoparticles and targeted therapies that utilize the unique bone marrow niche, are explored for their potential to enhance drug accumulation at metastatic sites while minimizing systemic toxicity. These approaches include the use of liposomes, polymeric nanoparticles, and inorganic nanoparticles, which can be functionalized to exploit the biological barriers within the bone microenvironment. This review also discusses the challenges and future directions for nano-DDS in clinical settings, emphasizing the need for multidisciplinary research to effectively integrate these technologies into standard care protocols.
Collapse
Affiliation(s)
- Mohamad Bakir
- Department of Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (M.B.); (M.A.M.)
| | - Ahmad Dawalibi
- Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (A.D.); (A.B.)
| | - Mohammad Alaa Mufti
- Department of Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (M.B.); (M.A.M.)
| | - Ayman Behiery
- Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (A.D.); (A.B.)
| | - Khalid S. Mohammad
- Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (A.D.); (A.B.)
| |
Collapse
|
16
|
Liang J, Wang P, Lin Y, Jia A, Tong F, Li Z. Advances in Photothermal Therapy for Oral Cancer. Int J Mol Sci 2025; 26:4344. [PMID: 40362580 PMCID: PMC12072920 DOI: 10.3390/ijms26094344] [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: 04/10/2025] [Revised: 04/28/2025] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
Oral cancer represents a critical global health issue, where traditional treatment modalities are often characterized by considerable adverse effects and suboptimal effectiveness. Photothermal therapy (PTT) offers an innovative method for tumor treatment, leveraging photothermal agents to convert light into hyperthermia, ultimately leading to tumor ablation. PTT offers unique advantages in treating oral cancer due to its superficial anatomical location and consequent accessibility to laser irradiation. PTT's advantage is further enhanced by its capacity to facilitate drug release and promote tissue regeneration. Consequently, the application of PTT for oral cancer has garnered widespread interest and has undergone rapid development. This review outlines advances in PTT for oral cancer, emphasizing strategies to improve efficacy and combination therapy approaches. The key challenges, including temperature control and long-term biosafety, are discussed alongside future directions. The review also encompasses PTT's role in managing oral potentially malignant disorders and postoperative defects, conditions intimately linked with oral cancer. We aim to provide guidance for emerging PTT research in oral cancer and to promote the development of precise and efficient treatment strategies.
Collapse
Affiliation(s)
- Jian Liang
- School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; (J.L.); (P.W.); (Y.L.); (A.J.)
- Jiangxi Provincial Key Laboratory of Oral Diseases, Nanchang 330006, China
- Jiangxi Provincial Clinical Research Center for Oral Diseases, Nanchang 330006, China
| | - Pei Wang
- School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; (J.L.); (P.W.); (Y.L.); (A.J.)
- Jiangxi Provincial Key Laboratory of Oral Diseases, Nanchang 330006, China
- Jiangxi Provincial Clinical Research Center for Oral Diseases, Nanchang 330006, China
| | - Yanfang Lin
- School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; (J.L.); (P.W.); (Y.L.); (A.J.)
- Jiangxi Provincial Key Laboratory of Oral Diseases, Nanchang 330006, China
- Jiangxi Provincial Clinical Research Center for Oral Diseases, Nanchang 330006, China
| | - Ao Jia
- School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; (J.L.); (P.W.); (Y.L.); (A.J.)
- Jiangxi Provincial Key Laboratory of Oral Diseases, Nanchang 330006, China
- Jiangxi Provincial Clinical Research Center for Oral Diseases, Nanchang 330006, China
| | - Fei Tong
- School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; (J.L.); (P.W.); (Y.L.); (A.J.)
- Jiangxi Provincial Key Laboratory of Oral Diseases, Nanchang 330006, China
- Jiangxi Provincial Clinical Research Center for Oral Diseases, Nanchang 330006, China
| | - Zhihua Li
- School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; (J.L.); (P.W.); (Y.L.); (A.J.)
- Jiangxi Provincial Key Laboratory of Oral Diseases, Nanchang 330006, China
- Jiangxi Provincial Clinical Research Center for Oral Diseases, Nanchang 330006, China
| |
Collapse
|
17
|
Markovic MD, Panic VV, Pjanovic RV. Polymeric Nanosystems: A Breakthrough Approach to Treating Inflammation and Inflammation Related Diseases. Biopolymers 2025; 116:e70012. [PMID: 40104970 DOI: 10.1002/bip.70012] [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: 09/25/2024] [Revised: 02/17/2025] [Accepted: 03/02/2025] [Indexed: 03/20/2025]
Abstract
Inflammation processes can cause mild to severe damage in the human body and can lead to a large number of inflammation-related diseases (IRD) such as cancer, neural, vascular, and pulmonary diseases. Limitations of anti-inflammatory drugs (AID) application are reflected in high therapeutic doses, toxicity, low bioavailability and solubility, side effects, etc. Polymeric nanosystems (PS) have been recognized as a safe and effective technology that is able to overcome these limitations by AID encapsulation and is able to answer to the specific demands of the IRD treatment. PS are attracting great attention due to their versatility, biocompatibility, low toxicity, fine-tuned properties, functionality, and ability for precise delivery of anti-inflammatory drugs to the targeted sites in the human body. This article offers an overview of three classes of polymeric nanosystems: a) dendrimers, b) polymeric micelles and polymeric nanoparticles, and c) polymeric filomicelles, as well as their properties, preparation, and application in IRD treatment. In the future, the number of PS formulations in clinical practice will certainly increase.
Collapse
Affiliation(s)
- Maja D Markovic
- Innovation Center of Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
| | - Vesna V Panic
- Innovation Center of Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
| | - Rada V Pjanovic
- Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
| |
Collapse
|
18
|
Uno K, Kubota E, Mori Y, Nishigaki R, Kojima Y, Kanno T, Sasaki M, Fukusada S, Sugimura N, Tanaka M, Ozeki K, Shimura T, Johnston RN, Kataoka H. Mesenchymal stem cell-derived small extracellular vesicles as a delivery vehicle of oncolytic reovirus. Life Sci 2025; 368:123489. [PMID: 39987955 DOI: 10.1016/j.lfs.2025.123489] [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: 10/16/2024] [Revised: 02/10/2025] [Accepted: 02/17/2025] [Indexed: 02/25/2025]
Abstract
AIM The oncolytic reovirus has demonstrated efficacy against various cancer types in preclinical and clinical studies. However, its anti-tumor activity is limited. This study aimed to develop a novel drug delivery system (DDS) using small extracellular vesicles (sEVs) derived from human adipose-derived mesenchymal stem cells to enhance the therapeutic potential of reovirus. MATERIALS AND METHODS sEVs, which offer distinct advantages over traditional systems such as nanoparticles due to their natural biocompatibility, low immunogenicity, ability to cross biological barriers, and cell-derived targeting properties, were engineered to encapsulate reovirus particles (sEVs-reo). The anti-tumor activity of sEVs-reo was evaluated using colorectal cancer cell lines HCT116 and SW480. Additionally, resistance to neutralizing antibodies, internalization by cancer cells, and efficacy against junctional adhesion molecule-A(JAM-A)-knockout colon cancer cells resistant to reovirus, generated via CRISPR/Cas9, were assessed. KEY FINDINGS sEVs-reo encapsulated reovirus particles effectively, and at a concentration of 0.5 μg/ml, reduced viable tumor cells by 60.3 % in HCT116 and 42.5 % in SW480. Remarkably, sEVs-reo exhibited significant efficacy even in the presence of neutralizing antibodies, including anti-σ1 antibodies and serum from reovirus-infected mice. sEVs-reo were rapidly internalized by cancer cells within 4 h while exhibiting reduced immunogenicity relative to reovirus, and demonstrated significant anti-tumor activity against JAM-A-deficient colon cancer cells. SIGNIFICANCE This study demonstrates that sEVs-reo can address key challenges associated with oncolytic virotherapy. These findings support potential of sEVs as a novel and effective DDS for reovirus in colon cancer treatment, while offering a versatile platform to enhance the efficacy of other oncolytic viruses.
Collapse
Affiliation(s)
- Konomu Uno
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Eiji Kubota
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan.
| | - Yoshinori Mori
- Department of Gastroenterology, Nagoya City University West Medical Center, Kita-ku, Nagoya 462-8508, Japan
| | - Ruriko Nishigaki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Yuki Kojima
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Takuya Kanno
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Makiko Sasaki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Shigeki Fukusada
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Naomi Sugimura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Mamoru Tanaka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Keiji Ozeki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Takaya Shimura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| | - Randal N Johnston
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
| |
Collapse
|
19
|
Zhao N, Shi Y, Liu P, Lv C. pH-responsive carbohydrate polymer-based nanoparticles in cancer therapy. Int J Biol Macromol 2025; 306:141236. [PMID: 39978518 DOI: 10.1016/j.ijbiomac.2025.141236] [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: 01/07/2025] [Revised: 02/01/2025] [Accepted: 02/16/2025] [Indexed: 02/22/2025]
Abstract
Using the specific features of the tumor microenvironment (TME) for the development and design of novel nanomaterials can improve the capacity in tumor suppression. One of the prominent features of the TME is the mild acidic pH. Therefore, the development of pH-responsive nanoparticles can lead to the release of cargo and therapeutics at the tumor site, improving the selectivity and specificity. The materials used for the development of nanoparticles should possess a number of unique features including biocompatibility and anti-cancer activity. Hence, a special attention has been directed towards the use of carbohydrate polymers in the development of nanoparticles. The carbohydrate polymers can develop smart nanoparticles respond to the pH in TME to increase targeting ability and provide controlled drug release. Such approach is also beneficial in decreasing the side effects of systemic chemotherapy. The pH-responsive nanoparticles developed from carbohydrate polymers can be also used for the combination chemotherapy/immunotherapy/phototherapy of cancer. Furthermore, these nanoparticles demonstrate theranostic application capable of cancer diagnosis and therapy. Further attention to the large-scale production, biocompatibility and long-term safety of carbohydrate polymer-based pH-responsive nanoparticles should be directed to improve the clinical translation in the treatment of cancer patients.
Collapse
Affiliation(s)
- Nanxi Zhao
- Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, China
| | - Yang Shi
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Pai Liu
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Chengzhou Lv
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China.
| |
Collapse
|
20
|
Gautam S, Joshi S, Jindal P, Patel P, Pal RR, Kumar M, Gupta GD, Kurmi BD. Recent doxorubicin-conjugates in cancer drug delivery: Exploring conjugation strategies for enhanced efficacy and reduced toxicity. Int J Pharm 2025; 675:125556. [PMID: 40187698 DOI: 10.1016/j.ijpharm.2025.125556] [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: 01/17/2025] [Revised: 03/21/2025] [Accepted: 04/01/2025] [Indexed: 04/07/2025]
Abstract
Doxorubicin is a first-line treatment of cancer that works on the mechanism of DNA intercalation and topoisomerase II poisoning. Since the 20th century, Doxorubicin has been used as a promising drug to treat several types of cancer, both solid or metastatic, including breast, thyroid, bladder, ovarian, or gastric cancer, etc. Even though it shows promising effects on cancer cells, it also shows its effects on healthy cells with cancerous cells, which leads to several severe side effects, such as cardiomyopathy, phlebitis, congestive heart failure (CHF), etc., which limits its usage in chemotherapy. Several research has focused on the targeted delivery of doxorubicin to cancerous cells to reduce side effects and improve efficacy. To optimize its anticancer potential, scientists have recently been developing nano-formulations and investigating various conjugations. The structure of doxorubicin consists of two primary functional groups that can be employed for conjugation with a variety of biomolecules, The first is the primary amine group in a sugar moiety, and the other one is the primary hydroxyl group in the aliphatic chain ring. In this paper, we have mentioned several conjugations of doxorubicin such as antibodies, nanoparticles, polymers, and phytochemical conjugations. Different studies regarding these conjugations are also mentioned, which represent promising strategies to optimize cancer treatment by minimizing side effects.
Collapse
Affiliation(s)
- Shreastha Gautam
- Department of Pharmaceutical Quality Assurance, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India
| | - Sachin Joshi
- Department of Pharmaceutical Quality Assurance, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India
| | - Priya Jindal
- Department of Pharmaceutical Quality Assurance, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India
| | - Preeti Patel
- Department of Pharmaceutical Chemistry, ISF College of Pharmacy, GT Road Moga-142001, Punjab, India.
| | - Ravi Raj Pal
- Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India
| | - Manish Kumar
- Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India
| | - Ghanshyam Das Gupta
- Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India
| | - Balak Das Kurmi
- Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India.
| |
Collapse
|
21
|
Ma S, Yao S, Li Y, Yang Y, Tong T, Zheng H, Ma B, Wei P, Di Z, Zhao B, Deng J. A pH-Responsive Polyetheretherketone Implant Modified with a Core-Shell Metal-Organic Framework to Promote Antibacterial and Osseointegration Abilities. Biomater Res 2025; 29:0188. [PMID: 40290761 PMCID: PMC12022397 DOI: 10.34133/bmr.0188] [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: 11/20/2024] [Revised: 03/12/2025] [Accepted: 03/20/2025] [Indexed: 04/30/2025] Open
Abstract
Polyetheretherketone (PEEK) is considered to be a potential material for oral implants due to its elastic modulus being similar to that of human cortical bone. However, the poor antibacterial, anti-inflammatory, and osseointegration properties of bioinert PEEK have hindered its clinical application. Therefore, this study designed and constructed a pH-responsive PEEK implant with a bilayer core-shell zeolitic imidazolate framework-8 (ZIF-8) structure loaded on its surface, with an antimicrobial peptide (KR12) encapsulated in the outer shell and an osteogenic peptide (osteogenic growth peptide ) encapsulated in its inner core. In this study, the bilayer core-shell ZIF-8 structure was confirmed to have pH-responsive properties. In vitro studies proved that the implant could promote bone marrow mesenchymal stem cells' proliferation and differentiation and the M1 phenotype to M2 phenotype conversion of RAW 264.7 and could inhibit bacterial adhesion and proliferation. By constructing rats' distal femur with/without infection models, it was further demonstrated that the novel implant could effectively inhibit bacterial adhesion and growth, inhibit inflammation, and promote peri-implant osseointegration, which was more substantial when the local area was infected and the pH was lower than that of normal tissue. Collectively, the results suggest that this novel pH-responsive PEEK implant loaded with a bilayer core-shell ZIF-8 structure is a promising peptide delivery implant system, which is well suited for dental applications and offers a potential solution for the prevention of infection during the early phase after implantation.
Collapse
Affiliation(s)
- Shiqing Ma
- Department of Stomatology,
The Second Hospital of Tianjin Medical University, Tianjin 300070, PR China
- Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, PR China
| | - Shiyu Yao
- Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, PR China
- Department of Periodontology,
Tianjin Medical University School and Hospital of Stomatology, Tianjin 300070, PR China
| | - Yumeng Li
- Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, PR China
- Department of Periodontology,
Tianjin Medical University School and Hospital of Stomatology, Tianjin 300070, PR China
| | - Yilin Yang
- Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, PR China
- Department of Periodontology,
Tianjin Medical University School and Hospital of Stomatology, Tianjin 300070, PR China
| | - Tianyi Tong
- Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, PR China
- Department of Periodontology,
Tianjin Medical University School and Hospital of Stomatology, Tianjin 300070, PR China
| | - Hong Zheng
- Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, PR China
- Department of Periodontology,
Tianjin Medical University School and Hospital of Stomatology, Tianjin 300070, PR China
| | - Beibei Ma
- Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, PR China
- Department of Periodontology,
Tianjin Medical University School and Hospital of Stomatology, Tianjin 300070, PR China
| | - Pengfei Wei
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing 102600, PR China
| | - Zhengyi Di
- College of Chemistry, Tianjin Key Laboratory of Structure and Performance for Functional Molecules,
Tianjin Normal University, Tianjin 300387, PR China
| | - Bo Zhao
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing 102600, PR China
| | - Jiayin Deng
- Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, PR China
- Department of Periodontology,
Tianjin Medical University School and Hospital of Stomatology, Tianjin 300070, PR China
| |
Collapse
|
22
|
Baek MJ, Hur W, Kashiwagi S, Choi HS. Design Considerations for Organ-Selective Nanoparticles. ACS NANO 2025; 19:14605-14626. [PMID: 40193849 DOI: 10.1021/acsnano.5c00484] [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: 04/09/2025]
Abstract
Nanoparticles (NPs) have been extensively researched for targeted diagnostic imaging and drug delivery, yet their clinical translation remains limited, with only a few achieving Food and Drug Administration approval. This limited success is primarily due to challenges in achieving precise organ- or tissue-specific targeting, which arise from off-target tissue accumulation and suboptimal clearance profiles. Herein we examine the critical role of physicochemical properties, including size, surface charge, shape, elasticity, hardness, and density, in governing the biodistribution, targetability, and clearance of NPs. We highlight recent advancements in engineering NPs for targeted imaging and drug delivery, showcasing both significant progress and the remaining challenges in the field of nanomedicine. Additionally, we discuss emerging tools and technologies that are being developed to address these challenges. Based on recent insights from materials science, biomedical engineering, computational biology, and clinical research, we propose key design considerations for next-generation nanomedicines with enhanced organ selectivity.
Collapse
Affiliation(s)
- Min-Jun Baek
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States
| | - Won Hur
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States
| | - Satoshi Kashiwagi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States
| | - Hak Soo Choi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States
| |
Collapse
|
23
|
Hong SM, Lee DJ, Lee DG, Yeom JH, Lee JW, Chung N. Gold nanoparticle resveratrol complex increases apoptosis in KRAS mutant pancreatic cancer cells. Sci Rep 2025; 15:13760. [PMID: 40258879 PMCID: PMC12012166 DOI: 10.1038/s41598-025-98124-7] [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: 06/30/2024] [Accepted: 04/09/2025] [Indexed: 04/23/2025] Open
Abstract
The KRAS G12D mutation is the most prevalent type of pancreatic cancer and is found in about 35% of patients. Numerous natural chemicals are frequently investigated in cancer treatment to decrease side effects. Resveratrol (RVT) is a polyphenol that can promote cancer cell apoptosis and improve chemotherapy efficacy in cancers. To enhance delivery rate and efficacy, the size of about 30 nm gold nanoparticles (GNPs) was synthesized and conjugated to resveratrol via polyvinylpyrrolidone (GRs) for high bioavailability. Compared to RVT and GNPs, GRs had less inflammatory response and less toxicity on RAW 264.7 cells. This suggests that the toxicity of resveratrol can be alleviated by conjugation with gold nanoparticles. The viability of the human pancreatic cancer cell line (AsPC-1) decreased in sequence of GRs > RVT > GNPs, suggesting an enhanced anticancer effect of the GRs compared to resveratrol (RVT) alone. In addition, the extent of apoptosis was much bigger with GRs compared to RVT and GNPs. The apoptotic effects were confirmed with cell cycle arrest and expression of apoptosis-related genes and proteins. Thus, GRs had a better extent of anticancer effect than RVT, suggesting that GRs be considered as one of the prospective anti-cancer drugs for pancreatic cancer treatment.
Collapse
Affiliation(s)
- Seung Myun Hong
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Deok Jae Lee
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Dong Gun Lee
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Jae Ho Yeom
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Jin-Woo Lee
- Medical Science Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea.
| | - Namhyun Chung
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
| |
Collapse
|
24
|
George S, Saju H, Jaikumar T, Raj R, Nisarga R, Sontakke S, Sangshetti J, Paul MK, Arote RB. Deciphering a crosstalk between biological cues and multifunctional nanocarriers in lung cancer therapy. Int J Pharm 2025; 674:125395. [PMID: 40064384 DOI: 10.1016/j.ijpharm.2025.125395] [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: 11/26/2024] [Revised: 02/08/2025] [Accepted: 02/21/2025] [Indexed: 03/17/2025]
Abstract
In recent years, the utilization of nanocarriers has significantly broadened across a diverse spectrum of biomedical applications. However, the clinical translation of these tiny carriers is limited and encounters hurdles, particularly in the intricate landscape of the tumor microenvironment. Lung cancer poses unique hurdles for nanocarrier design. Multiple physiological barriers hinder the efficient drug delivery to the lungs, such as the complex anatomy of the lung, the presence of mucus, immune responses, and rapid clearance mechanisms. Overcoming these obstacles necessitates a targeted approach that minimizes off-target effects while effectively penetrating nanoparticles/cargo into specific lung tissues or cells. Furthermore, understanding the cellular uptake mechanisms of these nano carriers is also essential. This knowledge aids in developing nanocarriers that efficiently enter cells and transfer their payload for the most effective therapeutic outcome. Hence, a thorough understanding of biological cues becomes crucial in designing multifunctional nanocarriers tailored for treating lung cancer. This review explores the essential biological cues critical for developing a flexible nanocarrier specifically intended to treat lung cancer. Additionally, it discusses advancements in nanotheranostics in lung cancer.
Collapse
Affiliation(s)
- Sharon George
- Centre for Nano and Material Sciences, Jain (Deemed to be) University, Jain Global Campus, Bangalore, Karnataka 562112, India
| | - Hendry Saju
- Centre for Nano and Material Sciences, Jain (Deemed to be) University, Jain Global Campus, Bangalore, Karnataka 562112, India
| | - Tharun Jaikumar
- Centre for Nano and Material Sciences, Jain (Deemed to be) University, Jain Global Campus, Bangalore, Karnataka 562112, India
| | - Reshma Raj
- Centre for Nano and Material Sciences, Jain (Deemed to be) University, Jain Global Campus, Bangalore, Karnataka 562112, India
| | - R Nisarga
- Centre for Nano and Material Sciences, Jain (Deemed to be) University, Jain Global Campus, Bangalore, Karnataka 562112, India
| | - Samruddhi Sontakke
- Centre for Nano and Material Sciences, Jain (Deemed to be) University, Jain Global Campus, Bangalore, Karnataka 562112, India
| | - Jaiprakash Sangshetti
- Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baugh, Aurangabad 431001, India
| | - Manash K Paul
- Department of Radiation Biology and Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, India; Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles (UCLA), 90095 CA, USA.
| | - Rohidas B Arote
- Centre for Nano and Material Sciences, Jain (Deemed to be) University, Jain Global Campus, Bangalore, Karnataka 562112, India; Dental Research Institute, School of Dentistry, Seoul National University, Gwanak-ku, Seoul 08826, Republic of Korea.
| |
Collapse
|
25
|
Beigrezaei A, Rafipour R. Design of casein-based nanocarriers for targeted delivery of daunorubicin to leukemia cells. Biotechnol Appl Biochem 2025; 72:287-294. [PMID: 39324205 DOI: 10.1002/bab.2662] [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: 02/12/2024] [Accepted: 08/24/2024] [Indexed: 09/27/2024]
Abstract
Daunorubicin (DAU) is a chemotherapy drug approved for the treatment of some cancers. However, the clinical compatibility of DAU is limited due to its lack of specificity and its highly toxic effects, which interfere with normal cells. This toxicity can be reduced with nanocarriers and targeted drug delivery systems. In this study, to develop the drug delivery of DAU, the surface of synthesized nanoparticles was modified by folic acid to target cancer cells optimally. Encapsulation of DAU in protein sodium caseinate (NaCAS) was done by adding calcium ions to bring the casein (CAS) in the solution to a micellar structure to synthesize dense nanoparticles. Fourier-transform infrared spectroscopy transmission, fluorescence spectroscopy, UV-Vis spectroscopy, field emission scanning electron microscopy, and zeta potential studies designed and distinguished the synthesized nanocomplexes. The results showed that CAS nanoparticles successfully encapsulated DAU, and the protein surface was targeted by folic acid. Light scattering analysis determined that the particles with a scattering index number of 306.0 and an average size of 8.117 nm were synthesized. The zeta potential of CAS micelles is more harmful than CAS nanoparticles. This is because calcium ions are added during the formation of CAS nanoparticles during the drug-loading stages. These studies prove that the synthesized "NaCAS-DAU" and "NaCAS-DAU-folic acid" complexes can be favorable carriers in the targeted drug delivery of cancer drugs.
Collapse
Affiliation(s)
- Ali Beigrezaei
- Department of Chemistry, Kermanshah Branch, Islamic Azad University, Kermanshah, Iran
| | - Ronak Rafipour
- Department of Chemistry, Kermanshah Branch, Islamic Azad University, Kermanshah, Iran
| |
Collapse
|
26
|
Shaik R, Mounika V, Begum S, Rajkumar A, Mallikarjun B, Sri Harshini V, Kolure R, Sreevani B, Thakur S. Monoclonal Antibodies in Clinical Trials for Breast Cancer Treatment. Monoclon Antib Immunodiagn Immunother 2025; 44:17-39. [PMID: 40171653 DOI: 10.1089/mab.2024.0018] [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: 04/04/2025] Open
Abstract
One of the most potent therapeutic and diagnostic agents in contemporary medicine is the monoclonal antibody (mAb). mAbs can perform a variety of tasks in breast cancer (BC), including identifying and delivering therapeutic medications to targets, preventing cell development, and suppressing immune system inhibitors including directly attacking cancer cells. mAbs are one of the most effective therapeutic options, particularly for HER2, but they have not been well studied for their use in treating other forms of BC, particularly triple negative breast tumors. Bispecific and trispecific mAbs have created new opportunities for more targeted specific efficacy, which has a positive impact on the viability of antigen specificity. They are more versatile and effective than other forms of treatment, emerging as most popular option for treating BC. However, mAbs have a limit in treatment due to certain adverse effects, including fever, shaking, exhaustion, headache, nausea, and vomiting, as well as rashes, bleeding, and difficulty breathing. To examine the current and prospective future capacities of mAbs with regard to the detection and treatment of BC, the present review highlights advantages and disadvantages of mAb approach.
Collapse
Affiliation(s)
- Rahaman Shaik
- School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Varikuppala Mounika
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad-501510, India
| | - Shireen Begum
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad-501510, India
| | - Agolapu Rajkumar
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad-501510, India
| | - Bathurasi Mallikarjun
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad-501510, India
| | - Vollala Sri Harshini
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad-501510, India
| | - Rajini Kolure
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad-501510, India
| | | | - Sneha Thakur
- Department of Pharmacognosy, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad-501510, India
| |
Collapse
|
27
|
Gao L, Tang Z, Xiao D, Chen X, Zhu Y. Prostate Cancer-Targeting Liposome Loaded with Zinc Ion-Coordinated Photosensitizer for Enhanced Chemo-Photodynamic Therapy. Pharmaceutics 2025; 17:448. [PMID: 40284443 PMCID: PMC12030104 DOI: 10.3390/pharmaceutics17040448] [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: 02/13/2025] [Revised: 03/07/2025] [Accepted: 03/13/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Prostate cancer (PCa) is the second most prevalent cancer in males globally, impacting one out of every six males. However, the therapeutic effect of chemotherapy on PCa is restricted. Methods: To address this, we developed a tumor-targeted multifunctional liposomal platform (PTX-PS/Zn@Lip-Apt) for zinc-enhanced chemo-photodynamic therapy of PCa. Co-delivery of PTX and an aggregation-induced emission photosensitizer (TPEDPD) enables combined chemotherapy and photody-namic therapy. Zinc ions were loaded into liposomes to improve the chemosensitivity of PCa to chemodrugs. Then, the AS1411 aptamer was further modified onto the sur-face of the liposome to enhance its tumor targeting ability. Moreover, to improve the cellular uptake efficiency of the nanoparticles, the photochemical internalization (PCI) strategy was also employed. Results: In vitro experiments indicated that aptamer conjugation and PCI application enhanced the cellular uptake and cytotoxicity of PTX/PS-Zn@Lip-Apt. The zinc ion enhanced cytotoxicity could also be found. In vivo experiments demonstrated the good antitumor effect and biosafety of PTX/PS-Zn@Lip-Apt. Conclusions: Our findings provide an important basis for innovatively applying zinc-enhanced combined chemo-photodynamic therapy in prostate cancer.
Collapse
Affiliation(s)
- Li Gao
- State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau 999078, China
- College of Pharmacy, Guilin Medical University, Guilin 541004, China;
| | - Zhisheng Tang
- The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, China
| | - Dongming Xiao
- College of Pharmacy, Guilin Medical University, Guilin 541004, China;
| | - Xu Chen
- College of Pharmacy, Guilin Medical University, Guilin 541004, China;
| | - Yizhun Zhu
- State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau 999078, China
| |
Collapse
|
28
|
Lee CE, Noh KM, Kim S, Hong J, Kim K. Recent Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Engineering Strategies for Precise Strike Therapy against Tumor. Biomater Res 2025; 29:0170. [PMID: 40110051 PMCID: PMC11922527 DOI: 10.34133/bmr.0170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/23/2025] [Accepted: 03/02/2025] [Indexed: 03/22/2025] Open
Abstract
Effective drug delivery relies on the selection of suitable carriers, which is crucial for protein-based therapeutics such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). One of the key advantages of TRAIL is its ability to selectively induce apoptosis in cancer cells excluding healthy tissues by binding to death receptors DR4 and DR5, which are highly expressed in various cancer cells. Despite this promise, the clinical application of TRAIL has been limited by its short half-life, limited stability, and inefficient delivery to tumor sites. To overcome currently available clinical and engineering approaches, a series of sophisticated strategies is required: (a) the design of biomaterial-mediated carriers for enhanced targeting efficacy, particularly via optimizing selected materials, composition, formulation, and surface modulation. Moreover, (b) development of genetically modified cellular products for augmented TRAIL secretion toward tumor microenvironments and (c) cell surface engineering techniques for TRAIL immobilization onto infusible cell populations are also discussed in the present review. Among these approaches, living cell-based carriers offer the distinct advantage of systemically administered TRAIL-functionalized cells capturing circulating tumor cells in the bloodstream, thereby preventing secondary tumor formation. This review provides insight into the development of novel TRAIL delivery platforms, discusses considerations for clinical translation, and suggests future directions and complementary strategies to advance the field of TRAIL-based cancer therapeutics.
Collapse
Affiliation(s)
- Chae Eun Lee
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
| | - Kyung Mu Noh
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
| | - Sungjun Kim
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
| | - Jiyeon Hong
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Kyobum Kim
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
| |
Collapse
|
29
|
Kubbara EA, Bolad A, Malibary H. Advances in Liposomal Interleukin and Liposomal Interleukin Gene Therapy for Cancer: A Comprehensive Review of Preclinical Studies. Pharmaceutics 2025; 17:383. [PMID: 40143046 PMCID: PMC11945541 DOI: 10.3390/pharmaceutics17030383] [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: 12/13/2024] [Revised: 01/16/2025] [Accepted: 01/27/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies. METHODS A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: ("liposomal interleukin" OR "liposome-encapsulated interleukin") AND ("gene therapy" OR "gene delivery") AND ("cancer" OR "tumor" OR "oncology") AND ("pre-clinical studies" OR "animal models" OR "in vitro studies". RESULTS Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35-50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes. CONCLUSIONS Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy.
Collapse
Affiliation(s)
- Eman A. Kubbara
- Clinical Biochemistry Department, Faculty of Medicine, Rabigh Branch, King Abdulaziz University, Rabigh 21911, Saudi Arabia
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, Al-Neelain University, Khartoum 11121, Sudan
| | - Ahmed Bolad
- Department of Microbiology and Unit of Immunology, Faculty of Medicine, Al-Neelain University, Khartoum 11121, Sudan
| | - Husam Malibary
- Department of Medicine, Faculty of Medicine, King Abdulaziz University, Rabigh 21911, Saudi Arabia
| |
Collapse
|
30
|
Raoufi A, Soleimani Samarkhazan H, Nouri S, Khaksari MN, Abbasi Sourki P, Sargazi Aval O, Baradaran B, Aghaei M. Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets. Clin Exp Med 2025; 25:73. [PMID: 40048037 PMCID: PMC11885342 DOI: 10.1007/s10238-025-01588-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Accepted: 02/03/2025] [Indexed: 03/09/2025]
Abstract
Graft-versus-host disease remains one of the most formidable barriers to the complete success of hematopoietic stem cell transplantation that has emerged as the curative approach for many hematopoietic malignancies because it affects quality of life and overall survival. Macrophages are among the important members of the immune system, which perform dual roles in GVHD as both therapeutic tools and targets. This review epitomizes the multifunctional role of macrophages in the pathophysiology of both acute and chronic GVHD. Macrophages play an important role in the early phase of GVHD because of their recruitment and infiltration into target organs. Furthermore, they polarize into two functionally different phenotypes, including M1 and M2. In the case of acute GVHD, most macrophages express the M1 phenotype characterized by the production of pro-inflammatory cytokines that contribute to tissue damage. In contrast, in chronic GVHD, macrophages tend toward the M2 phenotype associated with the repair of tissues and fibrosis. A critical balance among these phenotypes is central to the course and severity of GVHD. Further interactions of macrophages with other lymphocytes such as T cells, B cells, and fibroblast further determine the course of GVHD. Macrophage interaction associated with alloreactive T cells promotes inflammation. This is therefore important in inducing injuries of tissues during acute GVHD. Interaction of macrophages, B cell, fibroblast, and CD4+ T cells promotes fibrosis during chronic GVHD and, hence, the subsequent dysfunction of organs. These are some insights, while several challenges remain. First, the impact of the dominant cytokines in GVHD on the polarization of macrophages is incompletely characterized and sometimes controversial. Second, the development of targeted therapies able to modulate macrophage function without systemic side effects remains an area of ongoing investigation. Future directions involve the exploration of macrophage-targeted therapies, including small molecules, antibodies, and nanotechnology, which modulate macrophage behavior and improve patient outcomes. This underlines the fact that a profound understanding of the dual role of macrophages in GVHD is essential for developing new and more effective therapeutic strategies. Targeting macrophages might represent one avenue for decreasing the incidence and severity of GVHD and improving the success and safety of HSCT.
Collapse
Affiliation(s)
- Atieh Raoufi
- Department of Immunology, Student Research Committee, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
| | - Hamed Soleimani Samarkhazan
- Student Research Committee, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sina Nouri
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran
| | - Mohammad Navid Khaksari
- Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Parvaneh Abbasi Sourki
- Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
| | - Omolbanin Sargazi Aval
- Department of Hematology, Faculty of Allied Medical Sciences, Zabol University of Medical Sciences, Zabol, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Daneshghah Ave, Tabriz, Iran.
| | - Mojtaba Aghaei
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| |
Collapse
|
31
|
Cai J, Liao W, Wen J, Ye F, Nie Q, Chen W, Zhao C. Algae-derived polysaccharides and polysaccharide-based nanoparticles: A natural frontier in breast cancer therapy. Int J Biol Macromol 2025; 297:139936. [PMID: 39824414 DOI: 10.1016/j.ijbiomac.2025.139936] [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: 09/02/2024] [Revised: 01/01/2025] [Accepted: 01/14/2025] [Indexed: 01/20/2025]
Abstract
Breast cancer is the second leading cause of cancer-related mortality among women worldwide, with its progression closely tied to the tumor microenvironment. To address the limitations and adverse effects of conventional therapies, algal polysaccharides and their nanoparticle derivatives have emerged as promising and effective anti-breast cancer agents. These bioactive compounds, derived from algae, are distinguished by their natural origin, non-toxicity, and significant medical relevance. Notably, algal polysaccharide-based nanoparticles exhibit advantageous properties such as hydrophilicity, biodegradability, prolonged circulation, and selective accumulation in tumor tissues. This review explores the relationship between the structural attributes of algal polysaccharides and their therapeutic efficacy. It further highlights the advantages of algal polysaccharide-based nanoparticles as drug delivery systems, particularly their potential in tumor targeting and overcoming multidrug resistance, thereby providing a theoretical foundation for their application in breast cancer treatment.
Collapse
Affiliation(s)
- Jiaer Cai
- College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Wei Liao
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Jiahui Wen
- College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Fangting Ye
- College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Qing Nie
- College of Marine and Biology Engineering, Yancheng Institute of Technology, Yancheng 224000, China
| | - Weichao Chen
- College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
| | - Chao Zhao
- College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
| |
Collapse
|
32
|
Deng H, Chen J, Wang H, Liu R, Zhang Y, Chang H, Tung CH, Zhang W. Hijacking the hyaluronan assisted iron endocytosis to promote the ferroptosis in anticancer photodynamic therapy. Carbohydr Polym 2025; 351:123123. [PMID: 39779030 DOI: 10.1016/j.carbpol.2024.123123] [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: 10/09/2024] [Revised: 11/27/2024] [Accepted: 12/05/2024] [Indexed: 01/11/2025]
Abstract
Photodynamic therapy (PDT) eradicates tumor cells by the light-stimulated reactive oxygen species, which also induces lipid peroxidation (LPO) and subsequently ferroptosis, an iron-depended cell death. Ferroptosis has a tremendous therapeutic potential in cancer treatment, however, the ferroptosis efficiency is largely limited by the available iron in cells. Through hijacking the CD44-mediated iron endocytosis of hyaluronan (HA), here PDT with enhanced ferroptosis was realized by a HA@Ce6 nanogel self-assembled from HA, a photosensitizer Chlorin e6 (Ce6) and Fe3+ as cross-linkers. Taking advantages of HA's natural affinity towards CD44, HA@Ce6 enabled a targeted Ce6 delivery in CD44-overexpressed breast cancer cells and meanwhile enhanced iron uptake to "fuel" ferroptosis together with the light-stimulated LPO. Further, HA@Ce6 demonstrated an excellent anticancer PDT efficacy and ferroptosis induction in the murine 4 T1 xenograft model. This HA@Ce6 successfully exploited the role of HA in iron transport to sensitize ferroptosis, providing a potent strategy to facilitate the anticancer PDT.
Collapse
Affiliation(s)
- Hong Deng
- State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China
| | - Jiayu Chen
- State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China; Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Huimin Wang
- State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China
| | - Runmeng Liu
- State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China
| | - Yiyi Zhang
- State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China
| | - Hui Chang
- Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Ching-Hsuan Tung
- Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA
| | - Weiqi Zhang
- State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China.
| |
Collapse
|
33
|
Balakrishnan B, Sarojini BK, Dayananda BS, Raghu SV, Venugopal DM, Prabhu A. Tamarind seed gum-based hydrogel for the targeted delivery of imidazobenzothiazole sulfonamide derivative as an anticancer agent. Int J Biol Macromol 2025; 295:139665. [PMID: 39793781 DOI: 10.1016/j.ijbiomac.2025.139665] [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: 10/24/2024] [Revised: 12/20/2024] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
The current investigation intended to assess the controlled delivery of 7-sulfonamide-2-(4-methylphenyl) imidazo[2,1-b] [1, 3] benzothiazole an anticancer agent (ACA) by tamarind seed gum-based hydrogel; for its potential activity against hepatocellular carcinoma. The FTIR spectra, SEM, 13C NMR, PXRD, and TGA analyses evidenced the successful loading of ACA into the hydrogel system. The rheological testing conveyed the increase in the elastic nature of ACA-loaded hydrogel helping in an effective release. In-vitro delivery of ACA from the hydrogel matrix was maximum at pH 5.5 with controlled and prolonged release of 98.93 ± 1 % over 1680 min. The ACA-release kinetics was well-fitted to the Hill equation model (R2 = 0.9925), leading to a non-Fickian diffusion process (n = 0.5217). The tamarind seed gum-based hydrogel as a potential matrix for the oral administration of the ACA at hepatocellular carcinoma was envisaged and acute oral toxicity assessment on the Drosophila Melanogaster model indicated a high safety profile in-vivo. The ACA-loaded TG-g-poly (AMPS) system showed an enhanced anticancer activity with an IC50 value of 37.27 μg/mL than the ACA (IC50 = 44.75 μg/mL). Studies on the ACA-loaded hydrogel's ability to induce apoptosis in hepatocellular carcinoma cells further supported its anticancer effectiveness in-vitro.
Collapse
Affiliation(s)
- Bhavya Balakrishnan
- Department of Industrial Chemistry, Mangalore University, Mangalagangotri 574199, Karnataka, India
| | | | | | - Shamprasad Varija Raghu
- Division of Neuroscience, Yenepoya Research Centre (YRC), Yenepoya (Deemed to be University), Mangalore 575018, Karnataka, India
| | - Deepa Mugudthi Venugopal
- Neurogenetics lab, Department of Applied Zoology, Mangalore University, Mangalagangotri 574199, Karnataka, India
| | - Ashwini Prabhu
- Division of Cancer Research and Therapeutics (CaRT), Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 585018, Karnataka, India
| |
Collapse
|
34
|
Gupta S, Kaur R, Bhardwaj A, Parashar D. Multifunctional Nanomaterials: Recent Advancements in Cancer Therapeutics and Vaccines. Indian J Microbiol 2025; 65:51-68. [PMID: 40371018 PMCID: PMC12069785 DOI: 10.1007/s12088-024-01274-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 03/27/2024] [Indexed: 05/16/2025] Open
Abstract
Nanotechnology has revolutionized cancer detection and treatment, overcoming limitations of conventional methods. Imaging, targeting, and therapy moieties can all be combined in multifunctional nanoparticle systems to deliver the imaging or treatment modalities to the tumor in a targeted manner. These nanostructures can be engineered to create smart drug delivery systems for effective distribution and combinatorial therapy. Nanostructures made of biomolecules are naturally multifunctional and have a variety of biological functions that can be investigated for use in cancer nanomedicine. The supramolecular characteristics of biomolecules can be carefully engineered to create smart drug delivery systems that enable effective drug distribution to specific areas of the body as well as combinatorial therapy in a single design. Nanotechnology has also increased the efficiency of cancer vaccines, highlighting the future of tumor immunotherapy. Nanomaterials are often used as anti-cancer drugs or anti-inflammatory drugs due to their biosafety potential and enhanced bioavailability. By delivering targeted antigens and adjuvants, nanomaterials can improve vaccination efficacy and safety, preventing rapid degradation and prolonging antigen retention in lymphoid and tumor cells. We examine both organic and inorganic multifunctional nanomaterials in this review, emphasizing particular multifunctional properties in the context of cancer targeting, therapy, and vaccinations.
Collapse
Affiliation(s)
- Saurabh Gupta
- Department of Biotechnology, GLA University, Mathura, Uttar Pradesh 281406 India
| | - Rasanpreet Kaur
- Department of Biotechnology, GLA University, Mathura, Uttar Pradesh 281406 India
| | - Alok Bhardwaj
- Department of Biotechnology, GLA University, Mathura, Uttar Pradesh 281406 India
| | - Deepak Parashar
- Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226 United States
| |
Collapse
|
35
|
Bashir S, Iram G, Rafique S, Bashir M, Ghani T, Tanveer A, Khan S, Aftab A, Shah Q, Hassan SMU, Saeed S. Encapsulation of Moringa oleifera aqueous extract in silver chitosan metallopolymer nanocomposites for anti-cancer activity. Int J Biol Macromol 2025; 297:139683. [PMID: 39793809 DOI: 10.1016/j.ijbiomac.2025.139683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 12/04/2024] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
The growing interest in plant-derived compounds and synthesis of metallopolymer nanocomposites (MPNCs) especially silver chitosan nanocomposites (AgCS-NCs) emerges as a useful platform to encapsulate and deliver plant-based anticancer drugs. This work presents the synthesis of AgCS-NCs by using Moringa oleifera aqueous leaf extract (MOAE) and the effect of concentration of MOAE on physicochemical properties of AgCS-NCs followed by its anticancer effect on MCF-7 cell line. The results of UV-visible spectroscopy (UV-Vis) and Scanning electron microscopy (SEM) showed successful formation of AgCS-NCs. The formation of AgCS-NCs was confirmed by Fourier transform infrared (FTIR) spectroscopy. The average percentage of encapsulation efficiency (% EE) was calculated to be 60 %. The hydrodynamic size of AgCS-NCs using the Dynamic light scattering (DLS) technique was found to be 308 nm with an average percentage encapsulation efficiency of 60 %. The loaded microcarriers have shown significant cell viability for normal HEK-293 and also showed robust cytotoxicity against breast cancer (MCF-7) cell line (p < 0.001). It is concluded that Ag-CS-NCs utilizing MOAE are very effective and have significant potential against cancer cells without harming normal cells.
Collapse
Affiliation(s)
- Shazia Bashir
- Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences (PIEAS), P. O. Nilore, 45650 Islamabad, Pakistan.
| | - Ghazala Iram
- Department of Chemistry, PIEAS, P. O. Nilore, 45650 Islamabad, Pakistan
| | - Saima Rafique
- Department of Physics, Air University, 44000 Islamabad, Pakistan
| | - Muhammad Bashir
- Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences (PIEAS), P. O. Nilore, 45650 Islamabad, Pakistan
| | - Tayyaba Ghani
- Department of Metallurgy and Material Engineering, PIEAS, 45650 Islamabad, Pakistan
| | - Afifa Tanveer
- The University of Azad Jammu & Kashmir, 13100 Muzaffarabad, Pakistan
| | - Samreen Khan
- Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences (PIEAS), P. O. Nilore, 45650 Islamabad, Pakistan
| | - Ayesha Aftab
- Department of Nanomedicine, Houston Methodist Resales Institute, Houston, TX 77030, USA
| | - Qasim Shah
- Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22020 Abbottabad, Pakistan
| | | | - Shaukat Saeed
- Department of Chemistry, PIEAS, P. O. Nilore, 45650 Islamabad, Pakistan
| |
Collapse
|
36
|
Umadevi K, Sundeep D, Vighnesh AR, Misra A, Krishna AG. Current Trends and Advances in Nanoplatforms-Based Imaging for Cancer Diagnosis. Indian J Microbiol 2025; 65:137-176. [PMID: 40371042 PMCID: PMC12069201 DOI: 10.1007/s12088-024-01373-9] [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: 05/05/2024] [Accepted: 08/02/2024] [Indexed: 05/16/2025] Open
Abstract
The intersection of nanotechnology and biomedical imaging has ushered in a new era in the early detection and diagnosis of cancer which has revolutionized biomedical imaging by enhancing sensitivity, resolution, and targeting capability. This review presents a comprehensive overview of the latest developments and innovations in nanoplatforms-based imaging for cancer diagnosis, a burgeoning field that holds significant potential in improving cancer detection and treatment. Recently multimodal imaging techniques utilizing the unique properties of different types of nanoparticles are providing comprehensive diagnostic information. This multi-pronged approach allows for more precise tumor localization, size estimation, and growth rate calculation, offering a holistic view of the tumor and its environment. The primary focus of this review is on the recent progress in various types of nanoparticle-based imaging modalities, including optical, magnetic resonance, ultrasound, and nuclear imaging. Specific advancements in nanomaterial design for targeted imaging are highlighted, showing the improvement of precision targeting as an impact on the detection of cancer cells, even in early-stage tumors. A keen examination on the integration of diagnostic and therapeutic capabilities into single nano-based platforms for theranostics, underscoring their potential in personalized medicine is provided. The current challenges in the field, such as issues related to toxicity, biodistribution, and clearance of nanoparticles, and it explores ongoing research aimed at overcoming these hurdles. The growing body of research in this field highlights the promising future of nanoplatforms in improving the early detection and treatment of cancer.
Collapse
Affiliation(s)
- Kovuri Umadevi
- Department of Pathology, Government Medical College and Hospital, Khaleelwadi, Nizamabad, Telangana 503001 India
| | - Dola Sundeep
- Biomedical Research Laboratory, Department of Electronics and Communication Engineering, Indian Institute of Information Technology Design and Manufacturing, Jagannathagattu Hill, Kurnool, Andhra Pradesh 518008 India
| | - Alluru Raghavendra Vighnesh
- Department of Mechanical Engineering, Indian Institute of Technology (IIT-BHU) Varanasi, Varanasi, Uttar Pradesh 221005 India
| | - Aroonima Misra
- ICMR-National Institute of Pathology, Sadarjang Hospital Campus, Ansari Nagar West, New Delhi, Delhi 110029 India
| | - Alluru Gopala Krishna
- Department of Mechanical Engineering, Jawaharlal Nehru Technological University Kakinada, Nagamallithota, Kakinada, Andhra Pradesh 533003 India
| |
Collapse
|
37
|
Zhang Z, Tang Y, Luo D, Qiu J, Chen L. Advances in nanotechnology for targeting cancer-associated fibroblasts: A review of multi-strategy drug delivery and preclinical insights. APL Bioeng 2025; 9:011502. [PMID: 40094065 PMCID: PMC11910205 DOI: 10.1063/5.0244706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/24/2025] [Indexed: 03/19/2025] Open
Abstract
Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment by promoting tumor growth, immune evasion, and metastasis. Recently, drug delivery systems targeting CAFs have emerged as a promising long-term and effective approach to cancer treatment. Advances in nanotechnology, in particular, have led to the development of nanomedicine delivery systems designed specifically to target CAFs, offering new possibilities for precise and personalized cancer therapies. This article reviews recent progress in drug delivery using nanocarriers that target CAFs. Additionally, we explore the potential of combining multiple therapies, such as chemotherapy and immunotherapy, with nanocarriers to enhance efficacy and overcome drug resistance. Although many preclinical studies show promise, the clinical application of nanomedicine still faces considerable challenges, especially in terms of drug penetration and large-scale production. Therefore, this review aims to provide a fresh perspective on CAF-targeted drug delivery systems and highlight potential future research directions and clinical applications.
Collapse
|
38
|
Loscertales E, Mateo J, España S. A comparative study of sensitizers and liposome composition in radiation-induced controlled drug release for cancer therapy. J Liposome Res 2025; 35:64-75. [PMID: 39258993 DOI: 10.1080/08982104.2024.2401800] [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: 05/08/2024] [Revised: 09/02/2024] [Accepted: 09/03/2024] [Indexed: 09/12/2024]
Abstract
This study investigates drug-loaded liposomes designed for controlled release under ionizing radiation to refine cancer treatment precision. Liposomes as carriers enable targeted chemotherapy delivery, reducing healthy tissue damage risk. Liposomes containing poly- or mono-unsaturated fatty acids and various sensitizing agents were assessed for responsiveness to UV light and γ photon irradiation including rose bengal (RB), protoporphyrin IX (PPIX), verteporfin (VP), cercosporin (CERC) and hypericin (HYP). Carboxyfluorescein (CF) was used as a surrogate for drug release measurements. VP and PPIX induced rapid drug release and lipid peroxidation under UV light, while RB prompted quick drug release under UV light and a modest immediate release under γ irradiation, eventually reaching full release a few hours after irradiation, demonstrating dose-dependent effects. Smaller liposomes displayed accelerated release, emphasizing size-dependent kinetics. In vitro analyses evaluated radiosensitizing effects of RB-loaded liposomes. Clonogenic assays indicated that RB-filled liposomes had minimal direct radiobiological effects but increased indirect radiation damage, as shown by the curvature of the cell survival curve. Our study sheds light on factors influencing liposomal drug release under ionizing radiation, spotlighting RB as a promising radiosensitizer requiring further investigation for cancer therapy potential.
Collapse
Affiliation(s)
- E Loscertales
- Grupo de Física Nuclear, EMFTEL & IPARCOS, Universidad Complutense de Madrid, Madrid, Spain
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - J Mateo
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - S España
- Grupo de Física Nuclear, EMFTEL & IPARCOS, Universidad Complutense de Madrid, Madrid, Spain
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- Institute for Physical and Information Technologies "Leonardo Torres Quevedo", ITEFI, Spanish National Research Council (CSIC), Madrid, Spain
| |
Collapse
|
39
|
Datta S, Kronek J, Nadova Z, Timulakova L, Minarcikova A, Miskovsky P. Effect of polymer architecture on the properties and in vitro cytotoxicity of drug formulation: A case study with mono- and di-gradient amphiphilic poly(2-Oxazoline)s. Eur J Pharm Biopharm 2025; 208:114635. [PMID: 39855577 DOI: 10.1016/j.ejpb.2025.114635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 12/25/2024] [Accepted: 01/15/2025] [Indexed: 01/27/2025]
Abstract
Due to the straightforward single-step synthesis, amphiphilic gradient copoly(2-oxazoline)s are becoming more popular alternative to their block analogue for the development of next-generation drug delivery systems. Here, we investigated the influence of polymer architecture on the physiochemical and biological assessment of nanoformulations formed by the self-assembly of gradient copoly(2-oxazoline)s. Two different architectures were synthesized: hydrophilic-grad-hydrophobic (mono-gradient) and hydrophobic-grad-hydrophilic-grad-hydrophobic (di-gradient) which contained a hydrophilic monomer, 2-ethyl-2-oxazoline (EtOx) and a hydrophobic monomer, 2-phenyl-2-oxazoline (PhOx). Di-gradient copolymers self-assembled in the presence of a hydrophobic model drug, curcumin and formed monodispersed or slightly polydispersed nanoparticle solution. On the other hand, mono-gradient copolymers formed polydispersed nanoparticle solutions. Di-gradient copolymer was slightly more efficient to solubilize curcumin. Mono-gradient copolymer nanoparticle showed faster monomer chain exchange kinetics and comparatively less stability in the presence of serum albumin. At longer incubation times, faster drug release was observed from the mono-gradient copolymer nanoformulations. Cytotoxicity of free curcumin and curcumin loaded nanoparticles in cancer cell of U87 MG (human glioblastoma cell) was dose and time-dependent, whereby the significant cell death occurred after 48 h. Curcumin-loaded mono-gradient copolymer nanoparticles inhibited U87MG cancel cell growth to a large extent compared to the di-gradient copolymer nanoparticles.
Collapse
Affiliation(s)
- Shubhashis Datta
- Faculty of Science, Pavol Jozef Safarik University in Kosice, Park Angelinum 19, 040 01 Kosice, Slovakia.
| | - Juraj Kronek
- Department for Biomaterials Research, Polymer Institute of the Slovak Academy of Sciences, Dubravska cesta 9 845 41 Bratislava, Slovakia
| | - Zuzana Nadova
- Department of Biophysics, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5 041 54 Kosice, Slovakia
| | - Ludmila Timulakova
- Department of Biophysics, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5 041 54 Kosice, Slovakia
| | - Alzbeta Minarcikova
- Department for Biomaterials Research, Polymer Institute of the Slovak Academy of Sciences, Dubravska cesta 9 845 41 Bratislava, Slovakia
| | - Pavol Miskovsky
- Faculty of Science, Pavol Jozef Safarik University in Kosice, Park Angelinum 19, 040 01 Kosice, Slovakia; SAFTRA Photonics sro., Moldavska cesta 51 04011 Kosice, Slovakia
| |
Collapse
|
40
|
Figueroa Rosado MM, Muñoz Forti K, Rodríguez-Rodríguez P, Arroyo-Martínez G, Rodríguez-Irizarry VJ, Ruiz-Rivera A, Quinones-Rodriguez JI, Santiago-Cardona PG, Rodriguez Martinez OM, Almodovar S, Castro ME, Suárez Martínez E. Calcium Sulfide Nanoclusters Trigger DNA Damage and Induce Cell Cycle Arrest in Non-Small-Cell Lung Adenocarcinoma Cells. Int J Mol Sci 2025; 26:1665. [PMID: 40004132 PMCID: PMC11855498 DOI: 10.3390/ijms26041665] [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: 12/18/2024] [Revised: 01/17/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
Lung cancer remains the most common malignancy independent of sex. Here, we focused on unraveling the molecular mechanisms of CaS nanoclusters inducing cytotoxicity by investigating DNA damage, the cell cycle, oxidative stress, and cellular repair mechanisms in non-small-cell lung carcinoma (NSCLC) cells compared to healthy lung fibroblasts. Our previous studies have demonstrated the therapeutic potential of calcium sulfide (CaS) nanostructures in skin and breast cancer models, leading to a significant reduction in cancer cell proliferation. However, how CaS nanoclusters enhance their therapeutic effects on cancer cells while minimizing damage to healthy cells remains unknown. Our results show that CaS nanoclusters, once dissociated into Ca2+ and H2S in an acidic microenvironment, selectively allow extracellular calcium to enter, leading to an increase in free calcium entry, triggering oxidative stress and limiting DNA repair mechanisms in NSCLC. Furthermore, CaS nanoclusters selectively arrest NSCLC cells in the G0-G1 and S phases of the cell cycle without affecting healthy cells' cycles. Here, we also show that the selective effects of CaS nanoclusters on lung adenocarcinoma are less likely to be regulated by intrinsic apoptotic or mitochondrial pathways. They are, rather, caused by an increase in Ca2+ and ROS, causing double-stranded DNA breakages. This selectivity for malignant cells is pH-dependent because it occurs in the acidic microenvironment characteristic of these cells. Overall, this is the first piece of evidence that CaS disrupts genomic stability, prevents the replication of damaged cells, and ultimately influences cell fate decisions such as cell cycle arrest or cell death including mitotic catastrophe and necroptotic simultaneous events.
Collapse
Affiliation(s)
| | - Kevin Muñoz Forti
- Department of Biology, University of Puerto Rico, Ponce 00732, Puerto Rico
| | | | | | | | | | | | | | | | - Sharilyn Almodovar
- Department of Immunology & Molecular Microbiology, Texas Tech University Health Sciences Center, Lubock, TX 79430, USA
| | - Miguel E. Castro
- Department of Chemistry, University of Puerto Rico, Mayagüez 00680, Puerto Rico
| | - Edu Suárez Martínez
- Department of Biology, University of Puerto Rico, Ponce 00732, Puerto Rico
- Department of Basic Sciences, Ponce Health Sciences University, Ponce 00716, Puerto Rico
| |
Collapse
|
41
|
Mustafa MB, Lou J, Phillips MA, Turner RF, Baccile JA, Best MD. Development of ROS-triggered masked liposomes for activated cellular delivery using a charge balance strategy. Chem Commun (Camb) 2025; 61:3131-3134. [PMID: 39690974 PMCID: PMC11869113 DOI: 10.1039/d4cc06309k] [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] [Indexed: 12/19/2024]
Abstract
We report a charge balance strategy for reactive oxygen species (ROS)-triggered activation of liposome cell delivery by unmasking cationic membranes. Zeta potential experiments, microplate-based vesicle interaction assays, and cellular delivery studies confirmed that modification of anionic lipid 1 by ROS led to the uncaging of cationic liposomes, thereby driving cellular association.
Collapse
Affiliation(s)
- Mayesha B Mustafa
- Department of Chemistry, 1420 Circle Drive, Knoxville, TN 37996-1600, USA.
| | - Jinchao Lou
- Department of Chemistry, 1420 Circle Drive, Knoxville, TN 37996-1600, USA.
| | - Miranda A Phillips
- Department of Chemistry, 1420 Circle Drive, Knoxville, TN 37996-1600, USA.
| | - Robert F Turner
- Department of Chemistry, 1420 Circle Drive, Knoxville, TN 37996-1600, USA.
| | - Joshua A Baccile
- Department of Chemistry, 1420 Circle Drive, Knoxville, TN 37996-1600, USA.
| | - Michael D Best
- Department of Chemistry, 1420 Circle Drive, Knoxville, TN 37996-1600, USA.
| |
Collapse
|
42
|
Yuan H, Jiang M, Fang H, Tian H. Recent advances in poly(amino acids), polypeptides, and their derivatives in drug delivery. NANOSCALE 2025; 17:3549-3584. [PMID: 39745097 DOI: 10.1039/d4nr04481a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/14/2025]
Abstract
Poly(amino acids), polypeptides, and their derivatives have demonstrated significant potential as biodegradable biomaterials in the field of drug delivery. As degradable drug carriers, they can effectively load or conjugate drug molecules including small molecule drugs, nucleic acids, peptides, and protein-based drugs, enhancing the stability and targeting of the drugs in vivo. This strategy ultimately facilitates precise drug delivery and controlled release, thereby improving therapeutic efficacy and reducing side effects within the body. This review systematically describes the structural characteristics and preparation methods of poly(amino acids) and polypeptides, summarizes the advantages of poly(amino acids), polypeptides, and their derivatives in drug delivery, and detailedly introduces the latest advancements in this area. The review also discusses current challenges and opportunities associated with poly(amino acids), peptides, and their derivatives, and offers insights into the future directions for these biodegradable materials. This review aims to provide valuable references for scientific research and clinical translation of biodegradable biomaterials based on poly(amino acids) and peptides.
Collapse
Affiliation(s)
- Huilin Yuan
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen 361005, China.
| | - Mingxia Jiang
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen 361005, China.
| | - Huapan Fang
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen 361005, China.
- Shenzhen Research Institute of Xiamen University, Shenzhen 518000, China
| | - Huayu Tian
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen 361005, China.
| |
Collapse
|
43
|
Chen K, Yang H, Cai R. Microfluidics for Nanomedicine Delivery. ACS Biomater Sci Eng 2025; 11:774-783. [PMID: 39772433 DOI: 10.1021/acsbiomaterials.4c02052] [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: 01/11/2025]
Abstract
Nanomedicine is revolutionizing precision medicine, providing targeted, personalized treatment options. Lipid-based nanomedicines offer distinct benefits including high potency, targeted delivery, extended retention in the body, reduced toxicity, and lower required doses. These characteristics make lipid-based nanoparticles ideal for drug delivery in areas such as gene therapy, cancer treatment, and mRNA vaccines. However, traditional bulk synthesis methods for LNPs often produce larger particle sizes, significant polydispersity, and low encapsulation efficiency, which can reduce the therapeutic effectiveness. These issues primarily result from uneven mixing and limited control over particle formation during the synthesis. Microfluidic technology has emerged as a solution, providing precise control over particle size, uniformity, and encapsulation efficiency. In this mini review, we introduce the state-of-the-art microfluidic systems for lipid-based nanoparticle synthesis and functionalization. We include the working principles of different types of microfluidic systems, the use of microfluidic systems for LNP synthesis, cargo encapsulation, and nanomedicine delivery. In the end, we briefly discuss the clinical use of LNPs enabled by microfluidic devices.
Collapse
Affiliation(s)
- Kangfu Chen
- Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China
- Department of Biomedical Engineering, Northwestern University, Chicago, Illinois 60611, United States
| | - Hongfen Yang
- Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China
| | - Ren Cai
- Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Material Science and Engineering, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
| |
Collapse
|
44
|
Yu Y, Tao Y, Ma J, Li J, Song Z. Targeting the tumor microenvironment with mesenchymal stem cells based delivery approach for efficient delivery of anticancer agents: An updated review. Biochem Pharmacol 2025; 232:116725. [PMID: 39746456 DOI: 10.1016/j.bcp.2024.116725] [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: 09/02/2024] [Revised: 11/14/2024] [Accepted: 12/18/2024] [Indexed: 01/04/2025]
Abstract
Drug delivery to cancer cells continues to present a major therapeutic challenge. Mesenchymal stem cells (MSCs) possess an intrinsic ability to migrate specifically to tumor tissues, making them promising candidates for targeted drug delivery. Evidence from preclinical studies indicates that MSCs loaded with therapeutic anti-cancer agents exhibit considerable anti-tumor activity. Moreover, several clinical trials are currently evaluating their effectiveness in cancer patients. The integration of MSCs with synthetic nanoparticles (NPs) enhances their therapeutic potential, particularly through the use of cell membrane-coated NPs, which represent a significant advancement in the field. This review systematically investigates the tumor microenvironment, the sources of MSCs, the tumor homing mechanisms, and the methods of loading and releasing anticancer drugs from MSCs. Furthermore, cutting-edge strategies to improve the efficacy of MSCs based drug delivery systems (DDS) including the innovative use of MSC membrane coated nanoparticles have been discussed. The study concludes with an overview of the therapeutic use of MSCs as drug carriers, including a detailed analysis of the mechanisms by which MSCs deliver therapeutics to cancer cells, enabling targeted drug delivery. It aims to elucidate the current state of this approach, identify key areas for development, and outline potential future directions for advancing MSCs based cancer therapies.
Collapse
Affiliation(s)
- Yang Yu
- Department of Emergency and Critical Care, the Second Hospital of Jilin University, Changchun 130000, China
| | - Ying Tao
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130000, China
| | - Jingru Ma
- Department of Clinical Laboratory, the Second Hospital of Jilin University, Changchun 130000, China
| | - Jian Li
- Department of Emergency and Critical Care, the Second Hospital of Jilin University, Changchun 130000, China
| | - Zhidu Song
- Department of Ophthalmology, the Second Hospital of Jilin University, Changchun 130000, China.
| |
Collapse
|
45
|
Izadiyan Z, Misran M, Kalantari K, Webster TJ, Kia P, Basrowi NA, Rasouli E, Shameli K. Advancements in Liposomal Nanomedicines: Innovative Formulations, Therapeutic Applications, and Future Directions in Precision Medicine. Int J Nanomedicine 2025; 20:1213-1262. [PMID: 39911259 PMCID: PMC11794392 DOI: 10.2147/ijn.s488961] [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: 07/27/2024] [Accepted: 01/01/2025] [Indexed: 02/07/2025] Open
Abstract
Liposomal nanomedicines have emerged as a pivotal approach for the treatment of various diseases, notably cancer and infectious diseases. This manuscript provides an in-depth review of recent advancements in liposomal formulations, highlighting their composition, targeted delivery strategies, and mechanisms of action. We explore the evolution of liposomal products currently in clinical trials, emphasizing their potential in addressing diverse medical challenges. The integration of immunotherapeutic agents within liposomes marks a paradigm shift, enabling the design of 'immuno-modulatory hubs' capable of orchestrating precise immune responses while facilitating theranostic applications. The recent COVID-19 pandemic has accelerated research in liposomal-based vaccines and antiviral therapies, underscoring the need for improved delivery mechanisms to overcome challenges like rapid clearance and organ toxicity. Furthermore, we discuss the potential of "smart" liposomes, which can respond to specific disease microenvironments, enhancing treatment efficacy and precision. The integration of artificial intelligence and machine learning in optimizing liposomal designs promises to revolutionize personalized medicine, paving the way for innovative strategies in disease detection and therapeutic interventions. This comprehensive review underscores the significance of ongoing research in liposomal technologies, with implications for future clinical applications and enhanced patient outcomes.
Collapse
Affiliation(s)
- Zahra Izadiyan
- Department of Chemistry, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Misni Misran
- Department of Chemistry, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Katayoon Kalantari
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA
| | - Thomas J Webster
- Biomedical Engineering, Hebei University of Technology, Tianjin, People’s Republic of China
- School of Engineering, Saveetha University, Chennai, India
| | - Pooneh Kia
- Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | | | - Elisa Rasouli
- Department of Electrical and Electronics Engineering, Nanyang Technological University, Nanyang, Singapore
| | - Kamyar Shameli
- School of Medicine, Institute of Virology, Technical University of Munich, Munich, Germany
| |
Collapse
|
46
|
Theivendren P, Pavadai P, Veerachamy S, Palanisamy P, Kunjiappan S. Surface receptor-targeted protein-based nanocarriers for drug delivery: advances in cancer therapy. NANOTECHNOLOGY 2025; 36:122003. [PMID: 39847811 DOI: 10.1088/1361-6528/adad7a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 01/23/2025] [Indexed: 01/25/2025]
Abstract
Significant progress has been made in cancer therapy with protein-based nanocarriers targeted directly to surface receptors for drug delivery. The nanocarriers are a potentially effective solution for the potential drawbacks of traditional chemotherapy, such as lack of specificity, side effects, and development resistance. Peptides as nanocarriers have been designed based on their biocompatible, biodegradable, and versatile functions to deliver therapeutic agents into cancer cells, reduce systemic toxicity, and maximize therapy efficacy through utilizing targeted ligands such as antibodies, amino acids, vitamins, and other small molecules onto protein-based nanocarriers and thus ensuring that drugs selectively accumulate in the cancer cells instead of healthy organs/drug release at a target site without effects on normal cells, which inherently caused less systemic toxicity/off-target effect. Moreover, their intrinsic protein backbone naturally degradesin vivo, providing another level of safety over synthetic materials. Various issues like immunogenicity, mass production, and quality control must be addressed for widespread use. However, further studies are necessary to perfect protein engineering and improve drug loading, protein modification, and targeting. Thus, it can be concluded that protein-based nanocarriers targeted against the surface receptors would help achieve cancer management in a more focused manner, thus minimizing toxicity. The further development of these nanoparticles could bring a significant change in cancer treatment so that more personalized, targeted, and safe therapies would be available to all patients.
Collapse
Affiliation(s)
- Panneerselvam Theivendren
- Department of Pharmaceutical Chemistry & Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology & Advanced Studies, Pallavaram, Chennai 600117, India
| | - Parasuraman Pavadai
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M.S.R. Nagar, Bengaluru 560054, Karnataka, India
| | - Suganthan Veerachamy
- School of Electronics Engineering, Vellore Institute of Technology, Vellore 632014, Tamilnadu, India
| | - Ponnusamy Palanisamy
- School of Mechanical Engineering, Vellore Institute of Technology, Vellore 632014, Tamilnadu, India
| | - Selvaraj Kunjiappan
- Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, Tamil Nadu, India
| |
Collapse
|
47
|
Wang M, Yu F, Zhang Y. Present and future of cancer nano-immunotherapy: opportunities, obstacles and challenges. Mol Cancer 2025; 24:26. [PMID: 39827147 PMCID: PMC11748575 DOI: 10.1186/s12943-024-02214-5] [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: 09/24/2024] [Accepted: 12/25/2024] [Indexed: 01/22/2025] Open
Abstract
Clinically, multimodal therapies are adopted worldwide for the management of cancer, which continues to be a leading cause of death. In recent years, immunotherapy has firmly established itself as a new paradigm in cancer care that activates the body's immune defense to cope with cancer. Immunotherapy has resulted in significant breakthroughs in the treatment of stubborn tumors, dramatically improving the clinical outcome of cancer patients. Multiple forms of cancer immunotherapy, including immune checkpoint inhibitors (ICIs), adoptive cell therapy and cancer vaccines, have become widely available. However, the effectiveness of these immunotherapies is not much satisfying. Many cancer patients do not respond to immunotherapy, and disease recurrence appears to be unavoidable because of the rapidly evolving resistance. Moreover, immunotherapies can give rise to severe off-target immune-related adverse events. Strategies to remove these hindrances mainly focus on the development of combinatorial therapies or the exploitation of novel immunotherapeutic mediations. Nanomaterials carrying anticancer agents to the target site are considered as practical approaches for cancer treatment. Nanomedicine combined with immunotherapies offers the possibility to potentiate systemic antitumor immunity and to facilitate selective cytotoxicity against cancer cells in an effective and safe manner. A myriad of nano-enabled cancer immunotherapies are currently under clinical investigation. Owing to gaps between preclinical and clinical studies, nano-immunotherapy faces multiple challenges, including the biosafety of nanomaterials and clinical trial design. In this review, we provide an overview of cancer immunotherapy and summarize the evidence indicating how nanomedicine-based approaches increase the efficacy of immunotherapies. We also discuss the key challenges that have emerged in the era of nanotechnology-based cancer immunotherapy. Taken together, combination nano-immunotherapy is drawing increasing attention, and it is anticipated that the combined treatment will achieve the desired success in clinical cancer therapy.
Collapse
Affiliation(s)
- Man Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, 38 Dengzhou Road, Qingdao, 266021, China.
| | - Fei Yu
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, 38 Dengzhou Road, Qingdao, 266021, China
| | - Yuan Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, 38 Dengzhou Road, Qingdao, 266021, China
| |
Collapse
|
48
|
Jang B, Amirshaghaghi A, Choi J, Miller J, Issadore DA, Busch TM, Cheng Z, Tsourkas A. Enhanced Accumulation and Penetration of Magnetic Nanoclusters in Tumors Using an 8-Magnet Halbach Array Leads to Improved Cancer Treatment. ACS NANO 2025; 19:1794-1808. [PMID: 39749910 PMCID: PMC11735326 DOI: 10.1021/acsnano.4c16600] [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] [Indexed: 01/04/2025]
Abstract
Nanoparticles have gained attention as drug delivery vehicles for cancer treatment, but often struggle with poor tumor accumulation and penetration. Single external magnets can enhance magnetic nanoparticle delivery but are limited to superficial tumors due to the rapid decline in the magnetic field strength with distance. We previously showed that a 2-magnet device could extend targeting to greater tissue depths. Here, we improve on this approach by constructing an 8-magnet device arranged in an annular Halbach array, which facilitates radial outward movement of magnetic nanoparticles from the bore's center. Using chlorin e6-coated magnetic nanoclusters (Ce6 clusters) with densely packed cobalt-doped superparamagnetic iron oxide nanoparticles, we demonstrated nearly a 7-fold improvement in nanoparticle movement through a porous matrix compared to the 2-magnet approach. This resulted in enhanced magnetic resonance contrast, accumulation, and penetration of Ce6 clusters into 4T1 triple-negative breast tumors in mice, leading to improved photodynamic therapy and highlighting the potential therapeutic application of the 8-magnet device.
Collapse
Affiliation(s)
- Bian Jang
- Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 435 Skirkanich Hall, Philadelphia, PA 19104, United States
| | - Ahmad Amirshaghaghi
- Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 435 Skirkanich Hall, Philadelphia, PA 19104, United States
| | - Jeongmoon Choi
- Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Joann Miller
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States
| | - David A. Issadore
- Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 435 Skirkanich Hall, Philadelphia, PA 19104, United States
| | - Theresa M. Busch
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States
| | - Zhiliang Cheng
- Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 435 Skirkanich Hall, Philadelphia, PA 19104, United States
| | - Andrew Tsourkas
- Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 435 Skirkanich Hall, Philadelphia, PA 19104, United States
| |
Collapse
|
49
|
Varanko AK, Deshpande S, Li X, Chilkoti A. Binding Strength, Not Valency, Dictates Accumulation and Penetration of Affinity Targeted Macromolecules into Solid Tumors. Biomacromolecules 2025; 26:503-513. [PMID: 39729341 DOI: 10.1021/acs.biomac.4c01303] [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: 12/28/2024]
Abstract
The efficacy of tumor-targeted therapeutics, engineered to engage specific cellular receptors to promote accumulation and penetration, is strongly influenced by the carrier's affinity for its target and the valency of binding molecules incorporated into the carrier. Previous research has primarily focused on improving targeting by augmenting the number of binding proteins on the carrier, inadvertently raising avidity without isolating the individual effects of binding strength and valency. Herein, we precisely evaluate the impact of multivalency on tumor targeting with a recombinant approach to independently control valency, avidity, and size. Our findings reveal that constructs with equivalent binding strength exhibit comparable receptor engagement and tumor extravasation, regardless of valency. Moreover, excessive avidity adversely affected tumor accumulation and penetration, with the highest-avidity construct showing diminished exposure. These results indicate that overall binding strength, not valency, is the primary determinant of tumor targeting, providing valuable insights for designing effective macromolecular drug carriers.
Collapse
Affiliation(s)
- Anastasia K Varanko
- Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, United States
| | - Sonal Deshpande
- Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, United States
| | - Xinghai Li
- Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, United States
| | - Ashutosh Chilkoti
- Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, United States
| |
Collapse
|
50
|
Zahed Nasab S, Akbari B, Mostafavi E, Zare I. Chitosan nanoparticles in tumor imaging and therapy. FUNDAMENTALS AND BIOMEDICAL APPLICATIONS OF CHITOSAN NANOPARTICLES 2025:405-445. [DOI: 10.1016/b978-0-443-14088-4.00006-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|