Extracellular vesicles: rising stars among drug delivery systems?

Engineered extracellular vesicles (EVs) are increasingly being lauded as the next generation of drug delivery systems. Their intrinsic biological properties as well as their ability to transport therapeutic drug molecules have generated enormous enthusiasm. In this opinion paper, the author recaps that many of the properties now presented as unique advantages of engineered EVs, including biocompatibility, low toxicity, cargo-loading capacity, and surface functionalization, have long been established features of synthetic lipid vesicles. However, the major obstacles that have limited clinical translation of multifunctional liposomes, particularly targeted liposomes, are also likely to pose substantial challenges for engineered targeted EVs. Rather than viewing engineered EVs as a revolutionary new class of nanocarriers, the author proposes that their development should be guided by the successes and limitations of liposome technology. Studying the lessons learned from liposome technology may help prevent repeating historical mistakes and facilitate the rational development of clinically translatable EV-based therapeutics.