Bioengineering extracellular vesicles as novel nanocarriers towards brain disorders

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.