A non-drug chemotherapy-like synergizes with gas-/immunotherapy based on cancer cell membrane camouflage-functionalized nanoplatform

Traditional drug chemotherapy reveals numerous unsatisfactory aspects for malignant tumors that is prone to recurrence and metastasis, such as low therapy effect, systemic side effects, and multidrug resistance. Based on the above considerations, we herein propose a non-drug chemotherapy-like in synergy with gas-/immunotherapy strategy based on tumor cell membrane (M) coating Ferulic acid (FA)-L-Arg-ovalbumin (OVA) nanoparticles (F-L-O@M NPs). It is found that the non-drug of FA can efficiently induce cancer cell apoptosis via the Janus kinases/signal transducer and activator of transcription 3 (JAK/STAT3) signal pathway. Moreover, the generation of NO gas ascribed to the oxidation of L-Arg by H2O2, not only restricts the respiratory metabolism of mitochondria and reduces the generation of ATP, but also downregulates the expression of P-gp protein, exhibiting a superior synergistic with FA-mediated antineoplastic. More importantly, NO gas augments FA-induced tumor cell apoptosis and efficiently release tumor-associated antigens, which in synergy with OVA enables significant activation and recruits cytotoxic T lymphocytes to infiltrate in tumor tissues, further combining with immune checkpoint blockade antibody to trigger a long-term immune memory response, as well as anti-metastasis/recurrence. It is highly expected that such a non-drug chemotherapy-like strategy that combines with gas-/immunotherapy showing great promising in the clinical translational potential of nanomedicine.