人造外泌体治疗心肌梗死:应用现状及前景

Artificial exosomes in treatment of myocardial infarction:current status and prospects

背景:心肌梗死是目前最严重的心血管疾病之一,现有的临床治疗方案如溶栓治疗、经皮冠状动脉介入治疗和冠状动脉旁路移植术均无法完全恢复缺血造成的心肌损伤。干细胞来源的外泌体治疗心肌梗死是近年来的研究热点,但天然来源的外泌体产量少,获取难度大、耗时长、归巢效果不佳等限制了其临床应用。在这种情况下,构建人造外泌体作为天然外泌体的替代品已成为解决上述问题的有效策略。目的:阐述人造外泌体在治疗心肌梗死中的研究现状,将其分为半人造和全人造两种设计模式,就两种模式的研究进展及存在的问题展开讨论,最后对其在未来的临床应用做出评价和展望。方法:以“人造外泌体,心肌梗死,工程化”为中文检索词,以“artificial exosome,hybrid exosome,myocardial infarction,nanoparticle,drug delivery system”为英文检索词,检索PubMed和中国知网数据库的相关文献。检索时限重点为2017年1月至2022年12月,同时纳入部分经典远期文献。通过阅读文题和摘要进行初步筛选;排除重复性研究、低质量期刊及内容不相关的文献,最后纳入73篇文献进行综述。结果与结论:(1)通过半人造改造外泌体的方式,不论是靶向肽段的修饰、生物膜的杂交或是磁力物质的辅助,均改善了传统的外泌体疗法靶向性不足、驻留率低、易被网状内皮系统所清除等缺陷,提高了传统外泌体治疗心肌梗死的效率,但是这些改造策略存在修饰效率不明确、医学伦理以及生物毒性等方面的问题。(2)全人造仿生外泌体相对于外泌体的改造,其设计自由度较高,可以解决天然来源外泌体提取存储难度高、规模化生产局限等问题,然而全人造外泌体的改造策略目前仍缺少可靠的临床前数据支持与生物安全性的检测,尚未形成规模化生产所需的标准化流程,因此在应用到临床以前,作为替代天然外泌体的人造外泌体方案仍需要科研人员进行持续深入研究。

BACKGROUND:Myocardial infarction is one of the most serious cardiovascular diseases at present,and the existing clinical treatment options such as thrombolytic therapy,percutaneous coronary intervention and coronary artery bypass grafting cannot fully restore the myocardial damage caused by ischemia.Stem cell-derived exosomes for the treatment of myocardial infarction have been a hot research topic in recent years,but the low yield of natural-derived exosomes,the difficulty and time consuming nature of obtaining them,and the poor homing effect have limited their clinical application.In this context,the construction of artificial exosomes as an alternative to natural exosomes has become an effective strategy to solve the above problems.OBJECTIVE:To expound the research status of artificial exosomes in the treatment of myocardial infarction,and classify them into two design modes:semi-artificial and full-artificial,and discuss the research progress and problems of the two modes,finally,make the evaluation and prospect of its clinical application in the future.METHODS:PubMed and CNKI were searched for relevant articles with“artificial exosomes,myocardial infarction,engineering”in Chinese,and“artificial exosome,hybrid exosome,myocardial infarction,nanoparticle,drug delivery system”in English.The focus of the search was from January 2017 to December 2022,and some of the classic forward literature was included.A preliminary selection was conducted through reading titles and abstracts.Repetitive studies,low-quality journals and irrelevant articles were excluded.Finally,73 articles were included for review.RESULTS AND CONCLUSION:(1)By semi-artificially modifying exosomes,whether it is the modification of targeting peptides,hybridization of biofilms or the assistance of magnetic substances,traditional exosome therapies with insufficient targeting and low retention rate and easy to be cleared by the reticuloendothelial system have improved the efficiency of traditional exosome therapy for myocardial infarction.However,these strategies have problems such as unclear modification efficiency,medical ethics,and biotoxicity.(2)Fully artificial bionic exosomes have a higher degree of design freedom compared to exosome modification,which can solve the problems of high extraction and storage difficulties of exosomes of natural origin and limitations of large-scale production;however,this artificial exosome strategy still lacks reliable preclinical data support and biosafety testing,and has not yet formed a standardized process required for large-scale production;therefore,before applying to the clinic,the artificial exosome solution as an alternative to natural exosomes still needs continuous in-depth research by researchers.