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Despite noteworthy technological progress and promising preclinical trials, brain disorders are still the leading causes of death globally. Extracellular vesicles (EVs), nano-/micro-sized membrane vesicles carrying bioactive molecules, are involved in cellular communication. Based on their unique properties, including superior biocompatibility, non-immunogenicity, and blood-brain barrier (BBB) penetration, EVs can shield their cargos from immune clearance and transport them to specific site, which have attracted increasing interests as novel nanocarriers for brain disorders. However, considering the limitations of native EVs, such as poor encapsulation efficiency, inadequate targeting capability, uncontrolled drug release, and limited production, researchers bioengineer EVs to fully exploit the clinical potential. Herein, this review initially describes the basic properties, biogenesis, and uptake process of EVs from different subtypes. Then, we highlight the application of EVs derived from different sources for personalized therapy and novel strategies to construct bioengineered EVs for enhanced diagnosis and treatment of brain disorders. Besides, it also presents a systematic comparison between EVs and other brain-targeted nanocarriers. Finally, existing challenges and future perspectives of EVs have been discussed, hoping to bolster the research from benchtop to bedside.

Publication history
Copyright
Acknowledgements

Publication history

Received: 10 June 2022
Revised: 10 August 2022
Accepted: 15 August 2022
Published: 27 September 2022
Issue date: February 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

The authors acknowledge financial support from National Natural Science Foundation of China (Nos. 82274104, 81903557, and 82074024), Natural Science Foundation of Jiangsu Province (No. BK20190802), Young Elite Scientists Sponsorship Program by CACM (No. 2021-QNRC2-A01), Natural Science Foundation Youth Project of Nanjing University of Chinese Medicine (No. NZY81903557), College Students’ Innovative Entrepreneurial Training of Jiangsu Province (No. 202110315021), and College Students’ Innovative Entrepreneurial Training of Kangyuan School of Chinese Herbal Medicine of Nanjing University of Chinese Medicine (No. kyxysc12).

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