Surface-Engineered Extracellular Vesicles in Cancer Immunotherapy

SIMPLE SUMMARY: Extracellular vesicles are small membranous particles secreted by cells. Extracellular vesicles facilitate the transportation of biomolecules, such as protein, RNA, and DNA fragments, to communicate with neighboring and distant cells. Cancer cells use extracellular vesicles to hijack the immune system and induce cancer-promoting signals. Modifying extracellular vesicles using surface engineering tools allows the addition of biomolecules for targeted delivery, thus modulating the hijacked tumor immune microenvironment to improve therapeutic efficacy. This review article discusses extracellular vesicle modification strategies explicitly focusing on the approaches used for surface engineering. We revisit the work carried out on the surface-engineered extracellular vesicle and its application in immunomodulating tumor microenvironments for cancer immunotherapy. ABSTRACT: Extracellular vesicles (EVs) are lipid bilayer-enclosed bodies secreted by all cell types. EVs carry bioactive materials, such as proteins, lipids, metabolites, and nucleic acids, to communicate and elicit functional alterations and phenotypic changes in the counterpart stromal cells. In cancer, cells secrete EVs to shape a tumor-promoting niche. Tumor-secreted EVs mediate communications with immune cells that determine the fate of anti-tumor therapeutic effectiveness. Surface engineering of EVs has emerged as a promising tool for the modulation of tumor microenvironments for cancer immunotherapy. Modification of EVs’ surface with various molecules, such as antibodies, peptides, and proteins, can enhance their targeting specificity, immunogenicity, biodistribution, and pharmacokinetics. The diverse approaches sought for engineering EV surfaces can be categorized as physical, chemical, and genetic engineering strategies. The choice of method depends on the specific application and desired outcome. Each has its advantages and disadvantages. This review lends a bird’s-eye view of the recent progress in these approaches with respect to their rational implications in the immunomodulation of tumor microenvironments (TME) from pro-tumorigenic to anti-tumorigenic ones. The strategies for modulating TME using targeted EVs, their advantages, current limitations, and future directions are discussed.