Current understanding of extracellular vesicle homing/tropism

Extracellular vesicles (EVs) are membrane-enclosed packets released from cells that can transfer bioactive molecules from cell to cell without direct contact with the target cells. This transfer of molecules can activate consequential processes in the recipient cells, including cell differentiation and migration that maintain tissue homeostasis or promote tissue pathology. One controversial aspect of the EV's biology that holds therapeutic promise is their capacity to engage defined cells at specific sites. On the one hand, persuasive studies have shown that EVs express surface molecules that ensure their tissue localization and enable cell-specific interactions, as demonstrated using in vitro and in vivo analyses. Therefore, this feature of EV biology is under investigation in translational studies to control malignancies and deliver chemicals and bioactive molecules to combat several diseases. On the other hand, some studies have shown that EVs fail to traffic in hosts in a targeted manner, which questions the potential role of EVs as vehicles for drug delivery and their capacity to serve as cell-free biomodulators. In this review, the biology of EV homing/tropism in mammalian hosts is discussed, and the biological characteristics that may result in their controversial characteristics are brought to the fore.