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

  • Angew Chem Int Ed Engl. 2023 Mar 1;62(10):e202215307. doi: 10.1002/anie.202215307.
Binbin Ding  1 ,  Hao Chen  1  2 ,  Jia Tan  1  2 ,  Qi Meng  1  2 ,  Pan Zheng  1  3 ,  Ping'an Ma  1  2 ,  Jun Lin  1  2
Affiliations
  • 1. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
  • 2. School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China.
  • 3. Institute of Frontier and Interdisciplinarity Science and Institute of Molecular Sciences and Engineering, Shandong University, Qingdao, 266237, China.
PMID: 36629270 DOI: 10.1002/anie.202215307
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-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.
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