Technologies for the Surface Functionalization of Extracellular Vesicles

Extracellular vesicles (EVs) are biological nanovesicles secreted by the majority of cells and can be found in all kingdoms of life. EVs show promise in diagnostics and therapeutics owing to their intrinsic roles as intracellular couriers. Their low immunogenicity, long retention in circulation, high biocompatibility, and modifiability suggest possible applications as natural drug delivery vehicles. However, natural EVs exhibit tropism related to their cellular origins and lack highly tissue- or cell-specific targeting properties. Additionally, loading drugs or proteins into EVs is typically necessary for functionality. Thus, EV surface engineering is important for enhancing the therapeutic potential of EVs. To this end, various surface bioengineering approaches have been developed, with a few functionalized EVs planned for clinical trials. In this chapter, we summarize recent advances in EV surface functionalization and discuss the advantages and limitations to each strategy. Furthermore, we also propose future directions for accelerating the clinical use of these strategies.