中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (8): 2181-2198.doi: 10.4103/NRR.NRR-D-24-00243

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

工程化细胞外囊泡作为缺血性脑卒中的递送载体:线粒体递送的前景

  

  • 出版日期:2025-08-15 发布日期:2024-12-12

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke: a special outlook on mitochondrial delivery

Jiali Chen1, #, Yiyang Li1, #, Xingping Quan1 , Jinfen Chen1 , Yan Han1 , Li Yang2 , Manfei Zhou1 , Greta Seng Peng Mok3 , Ruibing Wang1, 4, Yonghua Zhao1, 4, *   

  1. 1 Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao Special Administrative Region, China;  2 Department of Pharmacy, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, China;  3 Department of Electrical and Computer Engineering, University of Macau, Taipa, Macao Special Administrative Region, China;  4 Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao Special Administrative Region, China
  • Online:2025-08-15 Published:2024-12-12
  • Contact: Yonghua Zhao, MD, yonghuazhao@um.edu.mo.
  • Supported by:
    This work was supported by the grants from University of Macau, China, Nos. MYRG2022-00221-ICMS (to YZ) and MYRG-CRG2022-00011-ICMS (to RW); the Natural Science Foundation of Guangdong Province, No. 2023A1515010034 (to YZ).

摘要:

细胞外囊泡是一种天然的纳米载药体,在体内具有良好的生物相容性,在缺血性脑卒中治疗中具有显著优势。然而,细胞外囊泡的分布不确定和快速清除阻碍了其给药效率。令人鼓舞的是,通过利用膜修饰或将治疗药物封装在细胞外囊泡中,可以大大提高其给药效率。此外,先前的研究强调,大尺寸细胞外囊泡的一个子集--微囊泡(MVs)能将线粒体运送到邻近细胞,有助于缺血性脑卒中后线粒体功能的恢复。小细胞外囊泡(sEVs)也被证明有能力转运线粒体成分,如蛋白质或脱氧核糖核酸,或其子成分,用于基于细胞外囊泡的缺血性脑卒中治疗。这篇综述对细胞外囊泡分离技术进行了比较分析,并概述了目前主流的细胞外囊泡的改造方法。鉴于治疗缺血性脑卒中的复杂性,还划分了适合治疗过程不同方面的各种细胞外囊泡改造方法。鉴于人们对线粒体输送的兴趣日益浓厚,文章还深入探讨了通过小细胞外囊泡和微囊泡转运线粒体组分或完整线粒体的可行性和现有研究成果,为缺血性脑卒中的治疗提供了一个全新的视角。

https://orcid.org/0000-0001-8714-0476 (Yonghua Zhao)

Abstract: Ischemic stroke is a secondary cause of mortality worldwide, imposing considerable medical and economic burdens on society. Extracellular vesicles, serving as natural nanocarriers 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.

Key words: delivery, engineering, extracellular vesicles, identification, ischemic stroke, isolation, mitochondria, targeting strategy, therapeutic effects