The status of extracellular vesicles as drug carriers and therapeutics

Abstract

Owing to their natural origin and biocompatibility, extracellular vesicles (EVs) are being recognized as next-generation vehicles for targeted drug delivery. Despite their potential as therapeutic carriers, EVs suffer from heterogeneity, low yields, limited cargo loading efficiency and rapid clearance by the mononuclear phagocyte system. Since the first EV-based clinical trial in 2005, more than 100 clinical trials have investigated the use of EVs as therapeutics and drug carriers. Despite this, no EV-based therapies have received regulatory approval to date. This gap between preclinical research activity and clinical translation underscores persistent scientific challenges and regulatory hurdles that continue to impede the advancement of EV-based therapeutics. In this Review, we examine the research articles published in the field between 2012 and 2024 (38,177 articles), highlighting key developments, persistent challenges and evolving assumptions. We review the current EV landscape and clinical trials, focusing on their organotropism and use as carriers for therapeutics. We compare their advantages and limitations in relation to other nanoparticles, such as lipid nanoparticles and liposomes, and examine how labelling strategies and cell sources influence EV biodistribution. Finally, we outline translational considerations for EV-based therapeutics and propose additional reporting standards, complementing the MISEV 2023 guidelines. Extracellular vesicles (EVs) are emerging as biocompatible carriers for targeted drug delivery, yet challenges in yield, cargo loading and biodistribution persist. In this Review, key trends from over a decade of research are analysed, comparing EVs with lipid-based systems and outlining strategies for improving therapeutic translation and reporting standards.