Converting extracellular vesicles into nanomedicine: loading and unloading of cargo

Extracellular vesicles (EVs) are membranous containers that are secreted by multiple cell types and actively transport biomolecules such as lipids, proteins, and nucleic acids to distant cells, thereby inflicting phenotypic changes. In addition to their use in disease diagnosis, EVs have emerged as powerful tools for disease treatment. Specifically, the natural transport capacity of EVs can be exploited for drug delivery purposes. In this review, we focus on the key technologies that are used to 'design' EVs for their use as biological delivery vehicles. We provide a comprehensive overview of (i) methods for the loading of EVs with therapeutic cargo, (ii) methods for EV surface functionalization to direct EVs to target cells, and (iii) methods to stimulate cargo release from EVs. Finally, we discuss the remaining and up-coming challenges for the clinical translation of EV-mediated drug delivery.