Extracellular vesicles-based drug delivery system for cancer treatment

Abstract The decrease in cancer mortality indicates an improvement in cancer treatment and management. One strategy that has been a focus in cancer treatment is development of drug delivery systems (DDS). Lipid-based nanoparticles (e.g. liposomes or micelles) has been used in current DDS as vehicles to transport active molecules. Extracellular vesicles (EVs), a new player in DDS, consist of lipid and thus, can be categorized as lipid-based nanoparticles. EVs are derived from cells and harbour various targeting molecules from their origin cells. Therefore, EVs are not foreign to the host immune system and may be more effective and efficient than other synthetic nanoparticles to target solid tumours with a minimum adverse effect, providing an exciting alternative for lipid-based DDS. Active molecules can be loaded into EV endogenously by exposing cells with active molecules to generate EVs carrying these molecules, or exogenous loading using physical or chemical methods. In this review, we summarise the recent developments of EV-based DDS where the choice of donor cells, drug cargo, loading methods, and administration routes are discussed. Further, consideration of the bioavailability and biodistribution of EVs, as well as current challenges concerning the potential biosafety issue and standardized up-scale production of EVs are highlighted.