Engineering and Precision Delivery Strategies of Functionalized Extracellular Vesicles for Antitumor Therapy

Nanomedicine harnesses the unique benefits of nanocarriers to markedly enhance drugs targeting tumors, which is becoming a promising approach to achieve precise and effective antitumor therapy. Extracellular vesicles (EVs), natural nanoscale entities, have garnered extensive attention due to their high biocompatibility and low immunogenicity. However, they often lack the specificity to identify and target lesion sites, leading to side effects when used systemically. Thus, modifying EVs to enhance their targeting ability is crucial. This review comprehensively elucidates the use of natural EVs in tumor treatment and functionalization strategies for EVs, including bioengineering modifications of parent cells, covalent and noncovalent modifications for the EV surface. The particular emphasis is placed on the precision delivery strategies of these functionalized EVs. According to the different delivery endpoints, they can be classified into tumor microenvironment delivery, intracellular delivery into tumor cells, and dual delivery to the tumor microenvironment and the tumor cell. Future perspectives focus on the essential aspects of constructing functionalized EVs and anticipate their evolving role in tumor-targeted therapies. Overall, this review offers a thorough analysis of recent advancements in functionalized EVs for antitumor therapy, providing valuable insights for their future development and precision biomedical applications.