ZIF‐8 Nanoparticles Evoke Pyroptosis for High‐Efficiency Cancer Immunotherapy

Abstract Although zeolitic imidazolate framework‐8 (ZIF‐8) has been applied in various tumor therapies, the intrinsic immunogenicity remains unclear. Here, we initiatively discover that ZIF‐8 nanoparticles (NPs) can intrinsically induce pyroptosis by a caspase‐1/gasdermin D (GSDMD)‐dependent pathway. The pyroptotic cell death is accompanied by necrosis and immunogenic cell death (ICD) simultaneously for efficient in situ immunity initiation. Meanwhile, carbonyl cyanide m‐chlorophenyl hydrazone (CCCP), a mitochondrial depolarizing agent, is successfully loaded into ZIF‐8 NPs and found to further enhance the pyroptosis process. Collectively, the obtained Pluronic F127‐modified CCCP‐incorporated ZIF‐8 NPs ( F127 ZIF‐8 CCCP NPs) activate antitumor immunity and reprogram immunosuppressive tumor microenvironment (TME), realizing high‐efficiency tumor growth inhibition. This work will facilitate biomedicine applications of ZIF‐8 and provide good inspiration for pyroptosis‐induced cancer therapy.