Exosomes in brain diseases: Mechanisms, advances, and perspectives

Abstract

The blood–brain barrier (BBB) remains a major biological obstacle limiting the effective delivery of therapeutics for central nervous system (CNS) disorders. Although conventional drug delivery approaches have achieved continuous advances, their clinical translation is frequently restricted by limited brain penetration, insufficient target specificity, and systemic adverse effects. Exosomes, endogenous extracellular vesicles (EVs) involved in intercellular communication, have emerged as promising candidates for CNS therapeutic delivery owing to their favorable biocompatibility, relatively low immunogenicity, and potential ability to interact with biological barriers. In this review, we first summarize the structural characteristics of the BBB and the mechanisms underlying exosome–BBB interactions and transport. We then discuss current strategies for exosome isolation, characterization, and engineering, highlighting how these approaches influence therapeutic performance and translational feasibility. Subsequently, we analyze recent advances in exosome-based therapies for major CNS disorders, including neurodegenerative diseases, brain tumors, and ischemic stroke, with emphasis on how distinct pathological environments guide the design of exosome cargos, targeting strategies, and functional modifications. Finally, we discuss key challenges associated with clinical translation, including manufacturing standardization, pharmacokinetic evaluation, safety assessment, and regulatory considerations. This review provides a pathology-driven and engineering-guided perspective for understanding the rational design and future development of exosome-based therapeutics for CNS disorders.