Engineered extracellular vesicles as brain therapeutics

Extracellular vesicles (EVs) are communication channels between different cell types in the brain, between the brain and the periphery and vice-versa, playing a fundamental role in physiology and pathology. The evidence that EVs might be able to cross the blood-brain barrier (BBB) make them very promising candidates as nanocarriers to treat brain pathologies. EVs contain a cocktail of bioactive factors, yet their content and surface can be further engineered to enhance their biological activity, stability and targeting ability. Native and engineered EVs have been reported for the treatment of different brain pathologies, although issues related to their modest accumulation and limited local therapeutic effect in the brain still need to be addressed. In this review, we cover the therapeutic applications of native and bioengineered EVs for brain diseases. We also review recent data about the interaction between EVs and the BBB and discuss the challenges and opportunities in clinical translation of EVs as brain therapeutics.