Biology and therapeutic potential of extracellular vesicle targeting and uptake

Extracellular vesicles (EVs) have gained significant attention owing to their role in pathophysiological processes and potential as therapeutic tools. EVs are small vesicles (30 nm-5 µm) containing specific cargo (proteins, nucleic acids and lipids) and are released from most cell types. Their capacity to target and induce phenotypical changes in recipient cells has established them as key mediators of intercellular communication. Although EV biogenesis is well studied, their uptake and fate in recipient cells are still poorly understood. In this Review, we focus on the cell biology underlying EV interactions with recipient cells and their intracellular fate. We discuss the mechanisms EVs use to achieve cell-specific targeting, cell signalling and functional cargo delivery and list the key challenges currently limiting our ability to harness these EVs into efficient therapeutic nanovehicles. We explore how our understanding of the molecular mechanisms supporting interactions of EVs with recipient cells and their functions herein can provide new strategies to use them for therapeutic approaches.