Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 36, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202204904
Keywords
Ca2+ Nanomodulators; Immunotherapy; Mitochondrial Ca2+ Overload; Pyroptosis
Categories
Funding
- National Natural Science Foundation of China [52050077, 51872263, 51720105015, 5192920116, 52102354, 52102180]
- Taishan Scholars Project [ts20190911]
- Major Basic Research Projects of Shandong Natural Science Foundation [ZR2020ZD36]
- Science and Technology Cooperation Project between Chinese and Australian Governments [2017YFE0132300]
- China Postdoctoral Science Foundation [2021M691919, 2021M703130]
- Postdoctoral Innovative Talents Support Program [BX2021360]
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Researchers have developed a pyroptosis inducer for cancer immunotherapy by inducing mitochondrial Ca2+ overload. The inducer triggers robust immune responses, effectively suppressing tumor proliferation and lung metastasis, providing new strategies and inspiration for pyroptosis-mediated cancer treatments.
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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