中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (2): 478-490.doi: 10.4103/NRR.NRR-D-24-00720

• 综述:退行性病与再生 • 上一篇    下一篇

神经退行性疾病中的外泌体：治疗潜力和修饰方法

  

  • 出版日期:2026-02-15 发布日期:2025-05-20
  • 基金资助:
    基金资助：本研究得到国家自然科学基金，编号：22103055；河北省自然科学基金，编号： F2024110001 ；河北省自然科学基金，编号：F2024110001；天津市光电探测技术与系统重点实验室开放课题，编号：2024LODTS215，2024LODTS216，2024LODTS216。

Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

Hongli Chen1, 2, *, Na Li2 , Yuanhao Cai2, 3, Chunyan Ma2 , Yutong Ye2 , Xinyu Shi2 , Jun Guo2 , Zhibo Han4 , Yi Liu2 , Xunbin Wei5, *   

  1. 1 Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China;  2 State Key Laboratory of Separation Membrane and Membrane Process & Tianjin Key Laboratory of Optoelectronic Detection Technology and Systems, School of Life Sciences, Tiangong University, Tianjin, China;  3 School of Intelligent Information Engineering, Medicine & Technology College of Zunyi Medical University, Zunyi, Guizhou Province, China;  4 Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceuticals, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin, China;  5 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Cancer Hospital & Institute, International Cancer Institute, Institute of Medical Technology, Peking University Health Science Center, Department of Biomedical Engineering, Peking University, Beijing, China
  • Online:2026-02-15 Published:2025-05-20
  • Contact: Hongli Chen, PhD, chenhli0107@163.com; Xunbin Wei, PhD, xwei@bjmu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 22103055 (to JG); the Natural Science Foundation of Hebei Province, No. F2024110001 (to HC); and Open Project of Tianjin Key Laboratory of Optoelectronic Detection Technology and System, Nos. 2024LODTS215 (to NL), 2024LODTS216 (to XS).

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摘要：

近年来，外泌体作为神经退行性疾病的治疗手段和早期诊断标志物的研究受到广泛关注。外泌体体积微小，能有效通过血脑屏障，靶向治疗脑深部病变。最近的研究表明，来自不同细胞的外泌体可通过调节各种炎症细胞因子、mRNA和病变蛋白的表达，从而参与神经退行性疾病的进展，发挥治疗作用。然而，外泌体由脂质双层膜组成，缺乏识别特异性靶细胞的能力，当它们与非特异性细胞相互作用时，这种局限性会导致副反应和毒性。逐渐增多的证据表明，表面修饰的外泌体具有更强的靶向性，可用作靶向给药载体，实现定点给药，在治疗神经退行性疾病方面显示出良好的效果。为此，文章对旨在阐明外泌体在神经退行性疾病中的治疗潜力和修饰方法的现有研究进行了最新综述发现，外泌体可以有效地穿过血脑屏障递送药物发挥治疗作用，也可以作为神经退行性疾病的早期诊断标志物；文章还介绍了增强外泌体靶向性的策略，如基因修饰、化学修饰(共价修饰：点击化学和代谢工程；非共价修饰：多价静电相互作用、配体-受体相互作用、疏水相互作用、基于适体的修饰和锚定CPO5肽的修饰)和纳米材料修饰，证实了外泌体对神经退行性疾病的治疗潜力。然而，外泌体在治疗神经退行性疾病的临床应用中也有一些亟待解决的问题，如应改进外泌体的制备、表征和优化方法，降低外泌体应用的副反应，而外泌体的应用范围和安全性还需要未来进一步研究和评估。

https://orcid.org/0000-0001-5580-707X (Hongli Chen); https://orcid.org/0000-0002-4269-9943 (Xunbin Wei)

关键词: 阿尔茨海默病, 细胞识别, 中枢神经系统疾病, 增强靶向, 外泌体修饰, 外泌体靶向, 神经退行性疾病, 帕金森病, 干细胞外泌体, 干细胞疗法

Abstract: In recent years, exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research. Exosomes are small and can effectively cross the blood–brain barrier, allowing them to target deep brain lesions. Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines, mRNAs, and disease-related proteins, thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects. However, exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells. This limitation can lead to side effects and toxicity when they interact with nonspecific cells. Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases. In this review, we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases. Our findings indicate that exosomes can efficiently cross the blood–brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases. We introduce the strategies being used to enhance exosome targeting, including genetic engineering, chemical modifications (both covalent, such as click chemistry and metabolic engineering, and non-covalent, such as polyvalent electrostatic and hydrophobic interactions, ligand-receptor binding, aptamer-based modifications, and the incorporation of CP05- anchored peptides), and nanomaterial modifications. Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases. However, several challenges remain in the clinical application of exosomes. Improvements are needed in preparation, characterization, and optimization methods, as well as in reducing the adverse reactions associated with their use. Additionally, the range of applications and the safety of exosomes require further research and evaluation.

Key words: Alzheimer’s disease, cell recognition, central nervous system diseases, enhanced targeting, exosome modification, exosome targeting, neurodegenerative disease, Parkinson’s disease, stem cell exosomes, stem cell therapy