Hybrid nanovesicle of chimeric antigen receptor (CAR)-engineered cell-derived vesicle and drug-encapsulated liposome for effective cancer treatment

Effective cancer therapeutics based on extracellular vesicles (EVs) require high-efficiency cancer-targeting and drug-encapsulation technology. Here, we demonstrate hybrid nanovesicles by fusing anti-epidermal growth factor receptor-chimeric antigen receptor-expressing cell-derived vesicles (anti-EGFR-CAR-CDVs) with drug-encapsulated liposomes for effective cancer treatment. HEK293 cells were genetically engineered with the anti-EGFR-CAR plasmid, and CAR-CDVs were produced by serial extrusion of the engineered cells. CAR-CDVs and drug-encapsulated liposomes were then efficiently fused to generate hybrid nanovesicles in 30% EtOH. This study employed a photosensitizer as a model drug for photodynamic therapy (PDT). The hybrid nanovesicles retained the CAR-CDV membrane proteins with a size of ∼ 170 nm. Indeed, photosensitizer-encapsulated hybrid nanovesicles could effectively target tumor cells and inhibit tumor growth upon laser irradiation. We believe that the proposed technology for the successful fusion of CDVs and liposomes can be used as a drug delivery platform with high tumor targeting and encapsulation efficiency.