Engineered cancer-derived small extracellular vesicle-liposome hybrid delivery system for targeted treatment of breast cancer

Cancer-derived small extracellular vesicles (sEVs) may be a promising drug delivery system that targets cancer cells due to their unique features, such as native homing ability, biological barrier crossing capability, and low immune response. However, the oncogenic cargos within them pose safety concerns, hence limiting their application thus far. We proposed using an electroporation-based strategy to extract the endogenous cargos from cancer-derived sEVs and demonstrated that their homing ability was still retained. A membrane fusion technique was used to fuse these sEVs with liposomes to form hybrid particles, which possessed both benefits of sEVs and liposomes. Anti-EGFR monoclonal antibodies were modified on the hybrid particles to improve their targeting ability further. The engineered hybrid particles showed higher drug loading ability that is 33.75 and 43.88% higher than that of liposomes and sEVs, respectively, and improved targeting ability by 52.23% higher than hybrid particles without modification. This delivery system showed >90% cell viability and enhanced treatment efficiency with 91.58 and 79.26% cell migration inhibition rates for the miR-21 inhibitor and gemcitabine, respectively.