载药外泌体在中枢神经系统疾病中的热点问题  

Hot topics on exosomes as drug delivery system in central nervous system diseases

作　　者：林慧洁 黄云 黄志华 江丽霞 Lin Huijie;Huang Yun;Huang Zhihua;Jiang Lixia(First Clinical Medical School of Gannan Medical University,Ganzhou 341000,Jiangxi Province,China;Key Laboratory of Ministry of Education for Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases,Gannan Medical University,Ganzhou 341000,Jiangxi Province,China;School of Basic Medicine,Gannan Medical University,Ganzhou 341000,Jiangxi Province,China;Clinical Laboratory of First Affiliated Hospital,Gannan Medical University,Ganzhou 341000,Jiangxi Province,China)

机构地区：[1]赣南医科大学第一临床医学院,江西省赣州市341000 [2]赣南医科大学心脑血管重点实验室,江西省赣州市341000 [3]赣南医科大学基础医学院,江西省赣州市341000 [4]赣南医科大学第一附属医院检验科,江西省赣州市341000

出　　处：《中国组织工程研究》2025年第23期5013-5021,共9页Chinese Journal of Tissue Engineering Research

基　　金：赣南医学院《心脑血管疾病防治教育部重点实验室》开放课题(XN201921),项目负责人:江丽霞;江西省卫健委项目(202130621),项目负责人:江丽霞;研究生创新专项资金项目(YC2023-S939),项目负责人:林慧洁;研究生创新专项资金项目(YC2022-S964),项目负责人:黄云。

摘　　要：背景:利用外泌体作为药物载体不仅可以精确靶向治疗部位,还能提高局部浓度,为药物进入中枢神经系统开辟了一条新途径。目的:探讨外泌体的生物发生、生物学功能,综述当前有关细胞外囊泡作为药物载体在中枢神经系统疾病治疗中的最新进展。方法:由第一作者检索Web of Science、Pub Med和中国知网数据库1976年1月至2024年1月发表的相关文献,以“exosomes,extracellular vesicles,central nervous system,drug delivery,ischemic stroke,Alzheimer’s disease,Parkinson’s disease,spinal cord injury,brain tumor”为英文检索词,以“外泌体,细胞外囊泡,中枢神经系统疾病,载药,脑卒中,阿尔兹海默病,帕金森病,脊髓损伤、脑肿瘤”为中文检索词,最终纳入94篇文献进行分析。结果与结论:(1)外泌体可以轻易通过血脑屏障输送蛋白质、代谢物和核酸到受体细胞中,调节细胞代谢。由于外泌体是由细胞分泌的小囊泡,具有更低的循环免疫原性,在体内循环中能够更少被巨噬细胞识别清除。(2)外泌体可以被设计为递送不同的治疗成分,包括RNA、蛋白质、化疗药物和免疫调节剂,能够将治疗成分传送至期望的目标。经过工程修饰的外泌体具有更好的靶向性,并且这种外泌体介导的传递免疫原性极低,有望为将来中枢神经系统疾病的精准治疗提供更加安全有效的方法。BACKGROUND:The use of exosomes as drug carriers can not only precisely target the therapeutic site,but also increase the local concentration,opening up a new way for drugs to enter the central nervous system.OBJECTIVE:To explore the biogenesis and biological functions of exosomes and summarize the current state-of-the-art regarding extracellular vesicles as drug carriers in the treatment of central nervous system diseases.METHODS:The first author searched Web of Science,PubMed,and CNKI for relevant literature from January 1976 to January 2024.The English search terms were“exosomes,extracellular vesicles,central nervous system,drug delivery,ischemic stroke,Alzheimer’s disease,Parkinson’s disease,spinal cord injury,brain tumor.”The Chinese search terms were“exosomes,extracellular vesicles,central nervous system diseases,drug delivery,stroke,Alzheimer’s disease,Parkinson’s disease,spinal cord injury,brain tumor.”Finally,94 articles were included for analysis.RESULTS AND CONCLUSION:(1)Exosomes can easily cross the blood-brain barrier and deliver proteins,metabolites,and nucleic acids to recipient cells to regulate cellular metabolism.Since exosomes are small vesicles secreted by cells,they have a much lower circulating immunogenicity and can be less likely to be recognized and cleared by macrophages in the internal circulation.(2)Exosomes can be engineered to deliver different therapeutically ingredients,including RNA,proteins,chemotherapeutic drugs,and immunomodulators,and are capable of delivering them to the desired target areas.Engineered modified exosomes have better targeting properties.Furthermore,this exosome-mediated delivery is extremely low in immunogenicity and is expected to provide a safer and more effective method for precision therapy of central nervous system diseases in the future.

关 键 词：中枢神经系统疾病 外泌体 药物递送 脑卒中 阿尔茨海默病 帕金森病 脊髓损伤 脑肿瘤 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R741