工程化间充质干细胞来源外泌体在靶向递送抗肿瘤药物中的应用与问题  

Application and problems in targeted delivery of antitumor drugs by exosomes derived from engineered mesenchymal stem cells

作　　者：王双敏 汪显耀 何志旭 Wang Shuangmin;Wang Xianyao;He Zhixu(Department of Immunology,Zunyi Medical University,Zunyi 563000,Guizhou Province,China;Key Cell Engineering Laboratory,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China;Ministry of Tissue Damage Repair and Regenerative Medicine Jointly Established a Collaborative Innovation Center,Zunyi Medical University,Zunyi 563000,Guizhou Province,China;Department of Pediatrics,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China)

机构地区：[1]遵义医科大学免疫学教研室,贵州省遵义市563000 [2]遵义医科大学附属医院贵州省细胞工程重点实验室,贵州省遵义市563000 [3]遵义医科大学组织损伤修复与再生医学省部共建协同创新中心,贵州省遵义市563000 [4]遵义医科大学附属医院儿科,贵州省遵义市563000

出　　处：《中国组织工程研究》2025年第23期4975-4983,共9页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(32270848),项目负责人:何志旭;国家自然科学基金资助项目(82360044),项目负责人:汪显耀;贵州省科技计划项目(黔科合基础-ZK[2022]一般607),项目负责人:汪显耀。

摘　　要：背景:间充质干细胞来源外泌体具有免疫原性低且肿瘤归巢能力强等优点,在靶向递送药物方面备受关注。但外泌体在到达靶细胞前易被体内循环迅速清除,此外,由于外泌体表面性质和摄取机制复杂,其靶向性并不十分明显,需要一定的工程化策略提高递送效率。目的:通过综述间充质干细胞来源外泌体工程化修饰的不同策略,了解提高外泌体递送效率的相关机制、临床前应用和面临的问题,为进一步临床应用提供理论依据。方法:检索中国知网、维普、万方、PubMed数据库从建库至2024年的相关文献,检索词为“间充质干细胞,外泌体,工程化外泌体,靶向递送,抗肿瘤药物”和“mesenchymal stem cells,exosomes,engineered exosomes,targeted delivery,antineoplastic agents”,筛选工程化间充质干细胞来源外泌体靶向递送抗肿瘤药物的文献,共计纳入85篇文献进行综述分析。结果与结论:(1)间充质干细胞来源外泌体的工程化修饰复杂多样,可通过显著增强外泌体对器官或组织靶向能力,增加血液循环中停留时间,以及降低外泌体中促肿瘤分子的表达,以此达到提高外泌体递送效率的效果;(2)间充质干细胞外泌体在目前的抗肿瘤治疗研究中递送传统和新型药物具有巨大前景;(3)当前仍然存在一些安全问题不能将其转化在临床中,未来的研究将进一步改进和深入研究递送机制,有望开发出更为高效和安全的治疗策略。BACKGROUND:Mesenchymal stem cell-derived exosomes inherit the advantages of low immunogenicity and strong tumor homing ability,garnering significant attention in targeted drug delivery.However,exosomes are prone to rapid clearance from the circulation before reaching target cells.Additionally,due to the complex surface properties and uptake mechanisms of exosomes,their targeting specificity is not distinctly apparent,necessitating engineered strategies to enhance delivery efficiency.OBJECTIVE:To elucidate mechanisms for enhancing the delivery efficiency of exosomes,preclinical applications,and challenges encountered by reviewing various approaches to engineering modifications of exosomes derived from mesenchymal stem cells so as to provide a theoretical basis for further clinical applications.METHODS:Relevant literature from the establishment of databases to 2024 was retrieved from databases including CNKI,VIP,WanFang,and PubMed.The search terms used were“mesenchymal stem cells,exosomes,engineered exosomes,targeted delivery,antineoplastic agents”in both English and Chinese.Literature focusing on engineered mesenchymal stem cell-derived exosomes for targeted delivery of antitumor drugs was screened,resulting in the inclusion of 85 articles for review and analysis.RESULTS AND CONCLUSION:(1)The engineering modification of mesenchymal stem cell-derived exosomes is complex and diverse.The delivery efficiency of exosomes can be improved by significantly enhancing their targeting ability to organs or tissues,increasing their residence time in the blood circulation,and reducing the expression of tumor-promoting molecules in exosomes.(2)Current examples of mesenchymal stem cell-derived exosome delivery of traditional and novel drugs demonstrate their tremendous potential.(3)There are still some safety issues that preclude their clinical translation.Future research will further improve and delve into the delivery mechanisms,with the hope of developing more efficient and safe therapeutic strategies.

关 键 词：间充质干细胞 外泌体 工程化外泌体 靶向递送 抗肿瘤药 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R363