Chen Hongli, Li Na, Cai Yuanhao, Ma Chunyan, Ye Yutong, Shi Xinyu, Guo Jun, Han Zhibo, Liu Yi, Wei Xunbin
Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
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.
Neural Regen Res. 2026 Feb 1;21(2):478-490. doi: 10.4103/NRR.NRR-D-24-00720. Epub 2024 Oct 22.
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 non-specific 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.
近年来，外泌体作为神经退行性疾病研究中的治疗剂和早期诊断标志物受到了广泛关注。外泌体体积小，能够有效穿过血脑屏障，使其能够靶向深部脑损伤。最近的研究表明，源自不同细胞类型的外泌体可能通过调节各种炎性细胞因子、mRNA和疾病相关蛋白的表达发挥治疗作用，从而阻止神经退行性疾病的进展并呈现有益效果。然而，外泌体由脂质双分子膜组成，缺乏识别特定靶细胞的能力。这种局限性在它们与非特异性细胞相互作用时可能导致副作用和毒性。越来越多的证据表明，表面修饰的外泌体具有增强的靶向能力，可作为靶向药物递送载体，在神经退行性疾病的治疗中显示出有前景的结果。在本综述中，我们提供了现有研究的最新概述，旨在设计修饰外泌体的方法并阐明它们在神经退行性疾病中的治疗潜力。我们的研究结果表明，外泌体能够有效地穿过血脑屏障以促进药物递送，并且还可以作为神经退行性疾病的早期诊断标志物。我们介绍了用于增强外泌体靶向性的策略，包括基因工程、化学修饰（共价修饰，如点击化学和代谢工程；非共价修饰，如多价静电和疏水相互作用、配体 - 受体结合、基于适配体的修饰以及CP05锚定肽的掺入）和纳米材料修饰。对这些策略的研究证实，外泌体在神经退行性疾病治疗中具有显著的治疗潜力。然而，外泌体的临床应用仍存在一些挑战。在制备、表征和优化方法方面以及减少与其使用相关的不良反应方面都需要改进。此外，外泌体的应用范围和安全性需要进一步研究和评估。
