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ZIF-8 Nanoparticles Evoke Pyroptosis for High-Efficiency Cancer Immunotherapy |
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| Authors: | Dr Binbin Ding Dr Hao Chen Dr Jia Tan Dr Qi Meng Dr Pan Zheng Prof Ping'an Ma Prof Jun Lin |
| Institution: | 1. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 China;2. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026 China;3. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 China Institute of Frontier and Interdisciplinarity Science and Institute of Molecular Sciences and Engineering, Shandong University, Qingdao, 266237 China |
| 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 (F127ZIF-8CCCP 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. |
| Keywords: | Immunogenic Cell Death Immunotherapy Necrosis Pyroptosis ZIF-8 Nanoparticle |