A high-valence bismuth(V) nanoplatform triggers cancer cell death and anti-tumor immune responses with exogenous excitation-free endogenous H2O2- and O2-independent ROS generation

Yizhang Tang, Xujiang Yu (), Liangrui He, Meng Tang, Wenji Yue, Ruitong Chen, Jie Zhao, Qi Pan and Wanwan Li ()
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Yizhang Tang: State Key Lab of Metal Matrix Composites School of Materials Science and Engineering Shanghai Jiao Tong University 800 Dongchuan Road
Xujiang Yu: State Key Lab of Metal Matrix Composites School of Materials Science and Engineering Shanghai Jiao Tong University 800 Dongchuan Road
Liangrui He: State Key Lab of Metal Matrix Composites School of Materials Science and Engineering Shanghai Jiao Tong University 800 Dongchuan Road
Meng Tang: Department of Comprehensive Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College 17 Panjiayuan South Lane
Wenji Yue: State Key Lab of Metal Matrix Composites School of Materials Science and Engineering Shanghai Jiao Tong University 800 Dongchuan Road
Ruitong Chen: State Key Lab of Metal Matrix Composites School of Materials Science and Engineering Shanghai Jiao Tong University 800 Dongchuan Road
Jie Zhao: State Key Lab of Metal Matrix Composites School of Materials Science and Engineering Shanghai Jiao Tong University 800 Dongchuan Road
Qi Pan: Department of Urology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine 85 Wujin Road
Wanwan Li: State Key Lab of Metal Matrix Composites School of Materials Science and Engineering Shanghai Jiao Tong University 800 Dongchuan Road

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Reactive oxygen species with evoked immunotherapy holds tremendous promise for cancer treatment but has limitations due to its dependence on exogenous excitation and/or endogenous H2O2 and O2. Here we report a versatile oxidizing pentavalent bismuth(V) nanoplatform (NaBiVO3-PEG) can generate reactive oxygen species in an excitation-free and H2O2- and O2-independent manner. Upon exposure to the tumor microenvironment, NaBiVO3-PEG undergoes continuous H+-accelerated hydrolysis with •OH and 1O2 generation through electron transfer-mediated BiV-to-BiIII conversion and lattice oxygen transformation. The simultaneous release of sodium counterions after endocytosis triggers caspase-1-mediated pyroptosis. NaBiVO3-PEG intratumorally administered initiates robust therapeutic efficacies against both primary and distant tumors and activates systemic immune responses to combat tumor metastasis. NaBiVO3-PEG intravenously administered can efficiently accumulate at the tumor site for further real-time computed tomography monitoring, immunotherapy, or alternative synergistic immune-radiotherapy. Overall, this work offers a nanomedicine based on high-valence bismuth(V) nanoplatform and underscores its great potential for cancer immunotherapy.

Date: 2025
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DOI: 10.1038/s41467-025-56110-7

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