Ultrasound‐Activated Ce(IV)‐Integrated Biomimetic Nanoplatform for Oxygenation‐Reinforced Gas‐Sonodynamic Ferroptosis and cGAS–STING‐Driven Antitumor Immunity
6 affiliations
- 1Cancer Research Center School of Medicine Xiamen University Xiamen People's Republic of China
- 2Department of Basic Medicine School of Medicine Xiamen University Xiamen People's Republic of China
- 3State Key Laboratory of Structural Chemistry CAS Key Laboratory of Design and Assembly of Functional Nanostructures Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences Fuzhou People's Republic of China
- 4School of Basic Medicine Fujian Medical University Fuzhou Fujian People's Republic of China
- 5Department of Hepatobiliary Surgery School of Medicine Xiang'an Hospital of Xiamen University Xiamen University Xiamen People's Republic of China
- 6School of Chemical Engineering Dalian University of Technology Dalian Liaoning People's Republic of China
Abstract
Immunologically “cold” tumors remain poorly responsive to immunotherapy because hypoxia‐limited oxidative therapy, insufficient immunogenic tumor‐cell death, and dysfunctional T‐cell responses restrict the transition from local tumor destruction to systemic antitumor immunity. Here, an ultrasound‐responsive Ce(IV)‐integrated biomimetic nanoplatform, TcEM@Ce‐P4CO@M, is developed to address these barriers. Ce4+/Ce3+ redox cycling promotes H2O2 decomposition and O2 generation, sustaining ultrasound‐triggered reactive oxygen species production under hypoxic conditions. Concurrently, P4CO‐derived carbon monoxide contributes to mitochondrial oxidative stress and lipid peroxidation. Endogenous iron‐homeostasis remodeling and impairment of the SLC7A11/glutathione (GSH)/glutathione peroxidase 4 (GPX4) antioxidant defense further favor ferroptosis‐associated tumor‐cell injury. Mitochondrial dysfunction and DNA damage are accompanied by enhanced stimulator of interferon genes (STING)‐associated signaling, while co‐delivered MSA‐2 further reinforces STING‐mediated innate immune activation, collectively contributing to an immunogenic environment that supports dendritic‐cell maturation. The engineered tumor‐derived membrane promotes tumor‐associated delivery and provides CD86‐mediated costimulation and anti‐TIM‐3‐mediated checkpoint modulation. In 4T1 tumor models, this coordinated cascade suppresses primary tumors, inhibits non‐irradiated distant tumors, reduces experimental pulmonary metastatic burden, and remodels the tumor immune microenvironment. Collectively, TcEM@Ce‐P4CO@M converts hypoxia‐limited local sonodynamic injury into ferroptosis‐linked innate‐to‐adaptive systemic antitumor immunity.
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BibTeX
@article{ma2026ultrasoundactivated,
title = {{Ultrasound‐Activated Ce(IV)‐Integrated Biomimetic Nanoplatform for Oxygenation‐Reinforced Gas‐Sonodynamic Ferroptosis and cGAS–STING‐Driven Antitumor Immunity}},
author = {Mengli Ma and Yingying Wu and Yunjie Wang and Yang Li and Yijia Zhang and Zhibo Zhang and Jinzhi Peng and Xiangyu Wu and Yi Luo and Weijing Zhang and Xin Ye and Weisong Lai and Shengyu Wang and Dan Du and Wengang Li and Nan Zheng and Fanghong Luo and Ting Wu},
journal = {Advanced Science},
year = {2026},
month = oct,
doi = {10.1002/advs.78187},
url = {https://doi.org/10.1002/advs.78187},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Ultrasound‐Activated Ce(IV)‐Integrated Biomimetic Nanoplatform for Oxygenation‐Reinforced Gas‐Sonodynamic Ferroptosis and cGAS–STING‐Driven Antitumor Immunity
AU - Mengli Ma
AU - Yingying Wu
AU - Yunjie Wang
AU - Yang Li
AU - Yijia Zhang
AU - Zhibo Zhang
AU - Jinzhi Peng
AU - Xiangyu Wu
AU - Yi Luo
AU - Weijing Zhang
AU - Xin Ye
AU - Weisong Lai
AU - Shengyu Wang
AU - Dan Du
AU - Wengang Li
AU - Nan Zheng
AU - Fanghong Luo
AU - Ting Wu
PY - 2026
DA - 2026/10/31
JO - Advanced Science
DO - 10.1002/advs.78187
UR - https://doi.org/10.1002/advs.78187
AB - Immunologically “cold” tumors remain poorly responsive to immunotherapy because hypoxia‐limited oxidative therapy, insufficient immunogenic tumor‐cell death, and dysfunctional T‐cell responses restrict the transition from local tumor destruction to systemic antitumor immunity. Here, an ultrasound‐responsive Ce(IV)‐integrated biomimetic nanoplatform, TcEM@Ce‐P4CO@M, is developed to address these barriers. Ce4+/Ce3+ redox cycling promotes H2O2 decomposition and O2 generation, sustaining ultrasound‐triggered reactive oxygen species production under hypoxic conditions. Concurrently, P4CO‐derived carbon monoxide contributes to mitochondrial oxidative stress and lipid peroxidation. Endogenous iron‐homeostasis remodeling and impairment of the SLC7A11/glutathione (GSH)/glutathione peroxidase 4 (GPX4) antioxidant defense further favor ferroptosis‐associated tumor‐cell injury. Mitochondrial dysfunction and DNA damage are accompanied by enhanced stimulator of interferon genes (STING)‐associated signaling, while co‐delivered MSA‐2 further reinforces STING‐mediated innate immune activation, collectively contributing to an immunogenic environment that supports dendritic‐cell maturation. The engineered tumor‐derived membrane promotes tumor‐associated delivery and provides CD86‐mediated costimulation and anti‐TIM‐3‐mediated checkpoint modulation. In 4T1 tumor models, this coordinated cascade suppresses primary tumors, inhibits non‐irradiated distant tumors, reduces experimental pulmonary metastatic burden, and remodels the tumor immune microenvironment. Collectively, TcEM@Ce‐P4CO@M converts hypoxia‐limited local sonodynamic injury into ferroptosis‐linked innate‐to‐adaptive systemic antitumor immunity.
SN - 2198-3844
ER -