Chen Jiali, Li Yiyang, Quan Xingping, Chen Jinfen, Han Yan, Yang Li, Zhou Manfei, Mok Greta Seng Peng, Wang Ruibing, Zhao Yonghua
Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao Special Administrative Region, China.
Department of Pharmacy, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, China.
Neural Regen Res. 2025 Aug 1;20(8):2181-2198. doi: 10.4103/NRR.NRR-D-24-00243. Epub 2024 Jul 29.
Ischemic stroke is a secondary cause of mortality worldwide, imposing considerable medical and economic burdens on society. Extracellular vesicles, serving as natural nano-carriers for drug delivery, exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke. However, the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency. By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles, their delivery efficacy may be greatly improved. Furthermore, previous studies have indicated that microvesicles, a subset of large-sized extracellular vesicles, can transport mitochondria to neighboring cells, thereby aiding in the restoration of mitochondrial function post-ischemic stroke. Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components, such as proteins or deoxyribonucleic acid, or their sub-components, for extracellular vesicle-based ischemic stroke therapy. In this review, we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies. Given the complex facets of treating ischemic stroke, we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process. Moreover, given the burgeoning interest in mitochondrial delivery, we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
缺血性中风是全球范围内导致死亡的次要原因，给社会带来了相当大的医疗和经济负担。细胞外囊泡作为药物递送的天然纳米载体，在体内表现出优异的生物相容性，在缺血性中风的治疗中具有显著优势。然而，细胞外囊泡分布的不确定性和快速清除阻碍了它们的递送效率。通过利用膜修饰或将治疗性货物包裹在细胞外囊泡内，它们的递送效果可能会大大提高。此外，先前的研究表明，微囊泡是大尺寸细胞外囊泡的一个子集，可以将线粒体运输到邻近细胞，从而有助于缺血性中风后线粒体功能的恢复。小细胞外囊泡也已证明能够转移线粒体成分，如蛋白质或脱氧核糖核酸，或它们的亚成分，用于基于细胞外囊泡的缺血性中风治疗。在这篇综述中，我们对用于分离细胞外囊泡的技术进行了比较分析，并概述了当前主要的细胞外囊泡修饰方法。鉴于治疗缺血性中风的复杂性，我们还描述了适合治疗过程不同方面的各种细胞外囊泡修饰方法。此外，鉴于对线粒体递送的兴趣日益浓厚，我们深入探讨了通过小细胞外囊泡和微囊泡运输线粒体组分或完整线粒体的可行性和现有研究结果，以为缺血性中风治疗提供新的视角。
