Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design

Extracellular vesicles (EVs) are submicron cell-secreted structures containing proteins, nucleic acids and lipids. EVs can functionally transfer these cargoes from one cell to another to modulate physiological and pathological processes. Due to their presumed biocompatibility and capacity to circumvent canonical delivery barriers encountered by synthetic drug delivery systems, EVs have attracted considerable interest as drug delivery vehicles. However, it is unclear which mechanisms and molecules orchestrate EV-mediated cargo delivery to recipient cells. Here, we review how EV properties have been exploited to improve the efficacy of small molecule drugs. Furthermore, we explore which EV surface molecules could be directly or indirectly involved in EV-mediated cargo transfer to recipient cells and discuss the cellular reporter systems with which such transfer can be studied. Finally, we elaborate on currently identified cellular processes involved in EV cargo delivery. Through these topics, we provide insights in critical effectors in the EV-cell interface which may be exploited in nature-inspired drug delivery strategies.