Engineering exosomes for precision tumor targeting to advance next-generation nanomedicine

Small extracellular vesicles (sEVs) are nanoscale (∼50–150 nm in diameter) membrane particles secreted by nearly all cell types that can be recovered easily from biofluids. sEVs mediate specific intercellular communication due to their selective molecular cargo of proteins, lipids, and nucleic acids and are mostly composed of vesicles that have an endosomal origin. Cancer tumor cells, in principle, could secrete sEVs to either promote tumor progression via cell proliferation, invasion, immunosuppression, or even boost antitumor responses. Among various types of vesicles, sEVs have an ideal combination of characteristics enabling them to be promising for oncology applications: inherent physiological stability in biological fluid, non-immunogenicity, and the capacity to target the tumor microenvironments intrinsically. For this reason, sEVs have become potential candidates for tumor diagnosis, prognosis, and progression detection as well as an engineered vehicle for cancer treatment. In this review, we summarize the latest developments in engineered sEVs for targeted therapy by analyzing their design and applications, in contrast to well-known artificial carriers, such as liposomes and lipid nanoparticles (LNPs). Moreover, we compare the therapeutic potential and limitations of sEV-therapeutics and present perspectives on their efficient utilization in recent studies.