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      Biodegradable Ca 2+ Nanomodulators Activate Pyroptosis through Mitochondrial Ca 2+ Overload for Cancer Immunotherapy

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          Abstract

          Pyroptosis provides a new direction and broad prospects for cancer immunotherapy. However, the development of a nanoplatform as a pyroptosis inducer is limited, and the discovery of a new type of nano-pyroptosis inducer for cancer immunotherapy is still imminent. Herein, biodegradable Ca2+ nanomodulators (CaNMs) are prepared as pyroptosis inducers for cancer immunotherapy via mitochondrial Ca2+ overload. The obtained CaNMs can decompose under low pH to release Ca2+ and curcumin, leading to a sudden surge in mitochondrial Ca2+ ions, eventually resulting in pyroptosis. We not only confirm the occurrence of mitochondrial Ca2+ overload-triggered pyroptosis for the first time but also reveal the robust immune responses via CaNMs, along with remarkably suppressing tumor proliferation and lung metastasis. This work will provide new strategies and inspiration for pyroptosis-mediated cancer treatments, greatly contributing to the further development of Ca2+ nanomodulators.

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          Author and article information

          Contributors
          Journal
          Angewandte Chemie International Edition
          Angew Chem Int Ed
          Wiley
          1433-7851
          1521-3773
          September 05 2022
          July 26 2022
          September 05 2022
          : 61
          : 36
          Affiliations
          [1 ]Institute of Molecular Sciences and Engineering Institute of Frontier and Interdisciplinary Science Shandong University Qingdao Shandong 266237 China
          [2 ]State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 China
          [3 ]University of Science and Technology of China Hefei 230026 P. R. China
          Article
          10.1002/anie.202204904
          35687022
          2364e7e2-33a8-4067-927e-881c502cded0
          © 2022

          http://onlinelibrary.wiley.com/termsAndConditions#vor

          http://doi.wiley.com/10.1002/tdm_license_1.1

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