Cell-derived nanovesicle-mediated drug delivery to the brain: Principles and strategies for vesicle engineering

Developing strategies toward safe and effective drug delivery into the central nervous system (CNS) with improved target-ing abilities and reduced off-target effects is crucial. CNS-targeted drug carriers made of synthetic molecules raise concerns about their biodegradation, clearance, immune responses, and neurotoxicity. Cell-derived nanovesicles (CDNs) have recently been applied in CNS-targeted drug de-livery, because of their intrinsic stability, biocompatibility, inherent homing capability, and the ability to penetrate through biological barriers, including the blood-brain barrier. Among these CDNs, extracellular vesicles and exosomes are the most studied because their surface can be engineered and modified to cater to brain targeting. In this review, we focus on the application of CDNs in brain-targeted drug de-livery to treat neurological diseases. We cover recently devel-oped methods of exosome derivation and engineering, including exosome-like particles, hybrid exosomes, exosome-associated adeno-associated viruses, and envelope protein nanocages. Finally, we discuss the limitations and project the future development of the CDN-based brain-targeted de-livery systems, and conclude that engineered CDNs hold great potential in the treatment of neurological diseases.

Automated summary

Developing strategies for safe and effective drug delivery into the CNS is crucial. Cell-derived nanovesicles (CDNs), particularly extracellular vesicles and exosomes, show promise as CNS-targeted drug carriers due to their stability, biocompatibility, homing ability, and ability to penetrate biological barriers. In this review, we focus on the application of CDNs in brain-targeted drug delivery, including recent methods of exosome derivation and engineering. We discuss the limitations and future development of CDN-based brain-targeted delivery systems, highlighting their potential in treating neurological diseases.