Engineered exosomes as precision tools for brain-targeted drug delivery and treatment of central nervous system diseases

Central nervous system diseases remain challenging due to the restrictive blood-brain barrier and the need for safe, effective brain-targeted delivery systems. Given their inherent biocompatibility, potential barrier penetration, and therapeutic cargo, exosomes have emerged as a transformative platform for brain drug delivery. However, native exosomes face limitations such as insufficient bioactivity and inadequate brain accumulation, impeding clinical efficacy and necessitating precision engineering. This review summarizes exosome biogenesis, cargo composition, and source-dependent heterogeneity to establish a foundation for therapeutic optimization. It also outlines cutting-edge exosome engineering strategies, detailing principles, techniques, strengths, and limitations to guide rational decision-making. Additionally, recent advances in engineered exosome-based therapies for central nervous system diseases are reviewed, focusing on optimizing critical delivery stages, covering therapeutic potency, brain biodistribution, and target cell selectivity. Future challenges and opportunities are discussed, aiming to accelerate the clinical adoption of engineered exosomes and advance precision paradigms for central nervous system disease treatment.