Engineering the future of nanomedicine: Strategic approaches to extracellular vesicle-based drug administration regimens.

As the role of extracellular vesicles (EVs) in stem cell therapy is increasingly recognized, more researchers regard them as a promising new natural delivery system. When exerting therapeutic effects, EVs exhibit several advantages, including low immunogenicity/cytotoxicity, the ability to traverse biological barriers, and high potential for engineering. However, several challenges remain in the clinical application of EVs. Their plasma half-life is relatively short, and they tend to accumulate in parenchymal organs (e.g., liver and spleen) within a short time. Moreover, their targeting capabilities are neither precise nor highly effective. Additionally, EVs lack controlled and sustained release properties, necessitating the design of effective delivery strategies to ensure that therapeutic concentrations are achieved and maintained at the target site for an adequate duration. This review summarizes the latest drug delivery strategies involving EVs, focusing on systemic and local applications. It introduces various engineering approaches, administration strategies, and auxiliary delivery systems. Finally, the review discusses existing challenges in EV-based drug delivery and provides insights into the trends for future development in this field.