Multifunctional Applications of Engineered Extracellular Vesicles in the Treatment of Cancer.

Extracellular vesicles (EVs) are key players of intercellular communication in the physiological and pathological setting. In cancer, EVs mediate complex signaling mechanisms between cancer cells and the tumor microenvironment (TME), and can influence tumor progression and the response to existing therapies. Importantly, EVs can be loaded with therapeutic agents and modified to display tumor-targeting molecules. In the field of nanomedicine, EVs have been engineered to serve as therapeutic delivery vehicles for several anticancer agents, including antibodies, chemotherapy, compounds, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated endonuclease 9), and small interfering RNA (siRNA). Notably, the engineered EVs were shown to suppress malignant features of cancer cells, to elicit antitumor immunity, and to decrease tumor angiogenesis. Here, we review the EV-based therapies designed to target cancer cells and to educate components of the TME to drive antitumor responses. These studies illustrate the multifunctional applications of EVs in the development of anticancer therapies and their translational potential for cancer treatment.