Applications of engineered tumor-derived extracellular vesicles in the treatment of cancer

Tumor-derived extracellular vesicles (TEVs) are a heterogeneous population of lipid bilayer membrane-enclosed vesicles. As a result of their natural properties to mediate cell-to-cell communication and their high physi-ochemical stability and biocompatibility, TEVs are considered an excellent carrier for a variety of therapeutic drugs such as nucleic acids and proteins, drugs, and nanomaterials. They have now emerged as a novel cell-free therapy for treating various diseases, including cancer. An increasing number of studies have shown that TEVs can be modified, engineered, or designed to improve cancer treatment efficiency, specificity, and safety. Here, we evaluate the available methods for TEVs loading and comprehensively review recent advances in strategies for surface-functionalized TEVs to achieve improved cargo loading and tumor targeting, as well as look forward to opportunities and challenges for translating engineered TEVs into clinical practice.