Enhancing cell pyroptosis with biomimetic nanoparticles for melanoma chemo-immunotherapy

Despite the fact that immunotherapy has significantly improved the prognosis of melanoma patients, the non-response rate of monoimmunotherapy is considerably high due to insufficient tumor immunogenicity . Therefore, it is necessary to develop alternative methods of combination therapy with enhanced antitumor efficiency and less systemic toxicity. In this study, we reported a cancer cell membrane-coated zeolitic imidazole framework-8 (ZIF-8) encapsulating pyroptosis-inducer oxaliplatin (OXA) and immunomodulator imiquimod (R837) for chemoimmunotherapy. With the assistance of DNA methyltransferase inhibitor decitabine (DCT), upregulated Gasdermin E (GSDME) was cleaved by OXA-activated caspase-3, further inducing tumor cell pyroptosis , then localized antitumor immunity was enhanced by immune adjuvant R837, followed by triggering systemic antitumor immune responses. These results provided a proof-of-concept for the use of cell membrane-coated biomimetic nanoparticles as a promising drug carrier of combination therapy and a potential insight for pyroptosis-based melanoma chemo-immunotherapy.