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

다국어 초록 (Multilingual Abstract)

Effective cancer therapeutics based on extracellular vesicles (EVs) require high-efficiency cancertargetingand drug-encapsulation technology. Here, we demonstrate hybrid nanovesicles by fusinganti-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 weregenetically engineered with the anti-EGFR-CAR plasmid, and CAR-CDVs were produced by serial extrusionof the engineered cells. CAR-CDVs and drug-encapsulated liposomes were then efficiently fused togenerate hybrid nanovesicles in 30% EtOH. This study employed a photosensitizer as a model drug forphotodynamic therapy (PDT). The hybrid nanovesicles retained the CAR-CDV membrane proteins witha size of 170 nm. Indeed, photosensitizer-encapsulated hybrid nanovesicles could effectively targettumor cells and inhibit tumor growth upon laser irradiation. We believe that the proposed technologyfor the successful fusion of CDVs and liposomes can be used as a drug delivery platform with high tumortargeting and encapsulation efficiency.