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基于外泌体的疗法:克服神经退行性疾病中血脑屏障的天然解决方案。

Exosome-Based Therapeutics: A Natural Solution to Overcoming the Blood-Brain Barrier in Neurodegenerative Diseases.

作者信息

Sun Min, Qin Feng, Bu Qian, Zhao Yue, Yang Xiaofeng, Zhang Dingwen, Cen Xiaobo

机构信息

Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy West China Hospital, Sichuan University Chengdu China.

出版信息

MedComm (2020). 2025 Sep 12;6(9):e70386. doi: 10.1002/mco2.70386. eCollection 2025 Sep.

Abstract

Neurodegenerative diseases present significant therapeutic challenges, primarily due to the restrictive nature of the blood-brain barrier (BBB), which limits drug delivery to the brain. While the BBB is crucial for protecting the brain from harmful substances, it also hinders the effectiveness of treatments for neurodegenerative diseases. Consequently, there is an urgent need for innovative drug delivery systems capable of bypassing the BBB to improve therapeutic outcomes. Exosomes, as endogenous nanoscale carriers, offer substantial promise for brain-targeted drug delivery. Their unique characteristics, including the ability to cross biological barriers, high biocompatibility, intrinsic targeting capacity, natural intracellular transport mechanisms, and robust stability, render them highly promising candidates for drug delivery in the treatment of neurodegenerative disorders. This review delves into various engineering strategies for exosome-mediated targeted drug delivery and provides an in-depth analysis of the structural and functional properties of the BBB under normal and pathological conditions. We emphasize the potential of exosomes as drug delivery vehicles for the central nervous system, particularly in addressing neurodegenerative disorders. Furthermore, we address the key obstacles to the clinical application of exosome-based therapies and propose future research directions aimed at optimizing these methods to develop more effective treatment strategies.

摘要

神经退行性疾病带来了重大的治疗挑战,主要是由于血脑屏障(BBB)的限制性质,它限制了药物向大脑的递送。虽然血脑屏障对于保护大脑免受有害物质侵害至关重要,但它也阻碍了神经退行性疾病治疗的有效性。因此,迫切需要能够绕过血脑屏障以改善治疗效果的创新药物递送系统。外泌体作为内源性纳米级载体,为脑靶向药物递送提供了巨大的前景。它们的独特特性,包括穿越生物屏障的能力、高生物相容性、内在靶向能力、天然细胞内运输机制以及强大的稳定性,使其成为神经退行性疾病治疗中药物递送的极有前景的候选者。本综述深入探讨了外泌体介导的靶向药物递送的各种工程策略,并对正常和病理条件下血脑屏障的结构和功能特性进行了深入分析。我们强调外泌体作为中枢神经系统药物递送载体的潜力,特别是在解决神经退行性疾病方面。此外,我们讨论了基于外泌体的疗法临床应用的关键障碍,并提出了未来的研究方向,旨在优化这些方法以开发更有效的治疗策略。

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