Mohamed J Saadh, Hanan Hassan Ahmed, Radhwan Abdul Kareem, Ashishkumar Kyada, H Malathi, Deepak Nathiya, Deepak Bhanot, Waam Mohammed Taher, Mariem Alwan, Mahmood Jasem Jawad, Atheer Khdyair Hamad
{"title":"Engineered Extracellular Vesicles for Targeted Paclitaxel Delivery in Cancer Therapy: Advances, Challenges, and Prospects.","authors":"Mohamed J Saadh, Hanan Hassan Ahmed, Radhwan Abdul Kareem, Ashishkumar Kyada, H Malathi, Deepak Nathiya, Deepak Bhanot, Waam Mohammed Taher, Mariem Alwan, Mahmood Jasem Jawad, Atheer Khdyair Hamad","doi":"10.1007/s12195-025-00858-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Scope: </strong>Extracellular vesicles (EVs) have emerged as promising cell-free delivery vehicles for cancer therapy due to their inherent biocompatibility, low immunogenicity, and natural targeting capabilities. EVs derived from various cellular sources offer distinct advantages in drug-loading capacity and therapeutic effectiveness. However, their clinical application is limited by challenges such as poor cargo stability, potential immunogenicity, and off-target effects. These limitations necessitate further surface functionalization of EVs to optimize vesicle stability, targeting precision, and safety of pharmacological cargos. Paclitaxel (PTX), a first-line chemotherapeutic agent effective against multiple cancers, is limited by poor solubility and significant systemic toxicity, highlighting the need for targeted delivery systems.</p><p><strong>Methods: </strong>A literature search was conducted to identify relevant articles published between 1993 and 2025. This review provides a comprehensive overview of EV biogenesis and cellular origins, highlighting recent advances in engineering strategies for PTX delivery. Current progress in employing engineered EVs for PTX delivery in both in vitro and in vivo cancer models, along with practical challenges and future directions in the clinical translation of EV-based PTX delivery, are discussed.</p><p><strong>Results: </strong>Preclinical studies demonstrate that engineered EVs can effectively encapsulate and deliver PTX to tumor sites, improving therapeutic outcomes while minimizing systemic side effects. Despite these advances, challenges remain in optimizing EV isolation, surface modification, PTX loading efficiency, and precise recognition of tumor cells.</p><p><strong>Conclusion: </strong>Engineered EVs represent a promising platform for PTX delivery, combining targeted therapeutic potential with reduced systemic toxicity. Continued research to address technical and translational barriers will be critical for advancing EV-based PTX therapies toward clinical application.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"213-237"},"PeriodicalIF":5.0000,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436268/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and molecular bioengineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s12195-025-00858-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOPHYSICS","Score":null,"Total":0}
引用次数: 0
Abstract
Scope: Extracellular vesicles (EVs) have emerged as promising cell-free delivery vehicles for cancer therapy due to their inherent biocompatibility, low immunogenicity, and natural targeting capabilities. EVs derived from various cellular sources offer distinct advantages in drug-loading capacity and therapeutic effectiveness. However, their clinical application is limited by challenges such as poor cargo stability, potential immunogenicity, and off-target effects. These limitations necessitate further surface functionalization of EVs to optimize vesicle stability, targeting precision, and safety of pharmacological cargos. Paclitaxel (PTX), a first-line chemotherapeutic agent effective against multiple cancers, is limited by poor solubility and significant systemic toxicity, highlighting the need for targeted delivery systems.
Methods: A literature search was conducted to identify relevant articles published between 1993 and 2025. This review provides a comprehensive overview of EV biogenesis and cellular origins, highlighting recent advances in engineering strategies for PTX delivery. Current progress in employing engineered EVs for PTX delivery in both in vitro and in vivo cancer models, along with practical challenges and future directions in the clinical translation of EV-based PTX delivery, are discussed.
Results: Preclinical studies demonstrate that engineered EVs can effectively encapsulate and deliver PTX to tumor sites, improving therapeutic outcomes while minimizing systemic side effects. Despite these advances, challenges remain in optimizing EV isolation, surface modification, PTX loading efficiency, and precise recognition of tumor cells.
Conclusion: Engineered EVs represent a promising platform for PTX delivery, combining targeted therapeutic potential with reduced systemic toxicity. Continued research to address technical and translational barriers will be critical for advancing EV-based PTX therapies toward clinical application.
期刊介绍:
The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas:
Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example.
Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions.
Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress.
Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.