A hybrid membrane coating nanodrug system against gastric cancer via VEGFR2/STAT3 signaling pathway

Although drug combination has been proved to be an efficient strategy for clinic gastric cancer therapy, how to further improve their bioavailability and reduce the side effects are still challenges due to the low solubility and untargeted ability of drugs. Recently, the new emerging nanotechnology provides an alternative for constructing new drug delivery system with high targeting ability and solubility. In this study, a pH-responsive liposomes (Liposome-PEO, LP) loading with apatinib (AP) and cinobufagin (CS-1) was used for combinational therapy against gastric cancer after coating with hybrid membrane (R/C). The results indicated that the constructed nanocomplexes LP-R/C@AC not only efficiently kill tumor cells in vitro through inducing apoptosis, autophagy and pyroptosis, but also significantly inhibit tumor invasion and metastasis via VEGFR2/STAT3 pathway. Moreover, it showed stronger anti-tumor activity in gastric cancer-bearing mouse models, compared to the sole drugs. Meanwhile, naturally derived hybrid cell membrane coating bestowed nanocomplexes with enhanced biointerfacing including prolonged circulation time and targeting ability.