An Activity‐Reinforced P‐Modified Single‐Atom Cu Nanozyme Potentiates IDO Blockade‐Induced Tumor Radiotherapy
6 affiliations
- 1Research Center of Nanomedicine Technology The Second Affiliated Hospital of Guangxi Medical University Nanning China
- 2Harbin Medical University Cancer Hospital Harbin China
- 3Department of Radiotherapy Cancer Center Aerospace Center Hospital Beijing China
- 4Department of Radiation Oncology Anhui No. 2 Provincial People's Hospital Hefei China
- 5State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer Tianjian Laboratory of Advanced Biomedical Sciences Academy of Medical Sciences Zhengzhou University Zhengzhou China
- 6CAS Engineering Laboratory For Nanozyme State Key Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing China
Abstract
Radiotherapy exerts both immunostimulatory and immunosuppressive effects on breast cancer (BRCA), limiting its therapeutic potential. To shift this balance toward a more favorable antitumor immune response, an indoleamine 2,3‐dioxygenase 1 (IDO1)‐blocking nanozyme specifically designed to potentiate tumor radioimmunotherapy was developed. Using a ZnO–carbon nanoframework, single Cu–N4 catalytic sites were engineered to construct a single‐atom Cu nanozyme (SAzyme) exhibiting dual peroxidase‐ and catalase‐mimicking activities for the delivery of the IDO1 inhibitor 1‐methyl‐tryptophan (1‐MT), resulting in a platform termed CPMR. Phosphorus modification further improved the catalytic performance of the SAzyme. Once internalized by tumor cells, CPMR generates sufficient oxygen to alleviate hypoxia and improve radiosensitivity while simultaneously inducing oxidative stress to promote tumor cell death and trigger immunogenic cell death. These events facilitate the recruitment and activation of tumor‐infiltrating cytotoxic T lymphocytes. The controlled release of 1‐MT inhibits IDO1 activity and reduces L‐tryptophan levels, suppressing regulatory T‐cell function and mitigating the immunosuppressive tumor microenvironment. These mechanisms synergistically improve the efficacy of radiotherapy against BRCA. CPMR represents a promising tumor‐reprogramming strategy capable of eliciting a robust antitumor immune response and significantly strengthening radiotherapeutic outcomes in patients with breast cancer.
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BibTeX
@article{zhao2026activityreinforced,
title = {{An Activity‐Reinforced P‐Modified Single‐Atom Cu Nanozyme Potentiates IDO Blockade‐Induced Tumor Radiotherapy}},
author = {Wei Zhao and Songliu Hu and Zhanggui Wang and Liqun Wang and Liming Zhang and Qi Li and Hua Tang and Yang Zhong and Zhongxian Zhang and Kelong Fan and Shipeng Ning and Xiyun Yan},
journal = {Advanced Science},
year = {2026},
month = oct,
doi = {10.1002/advs.202524253},
url = {https://doi.org/10.1002/advs.202524253},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An Activity‐Reinforced P‐Modified Single‐Atom Cu Nanozyme Potentiates IDO Blockade‐Induced Tumor Radiotherapy
AU - Wei Zhao
AU - Songliu Hu
AU - Zhanggui Wang
AU - Liqun Wang
AU - Liming Zhang
AU - Qi Li
AU - Hua Tang
AU - Yang Zhong
AU - Zhongxian Zhang
AU - Kelong Fan
AU - Shipeng Ning
AU - Xiyun Yan
PY - 2026
DA - 2026/10/31
JO - Advanced Science
DO - 10.1002/advs.202524253
UR - https://doi.org/10.1002/advs.202524253
AB - Radiotherapy exerts both immunostimulatory and immunosuppressive effects on breast cancer (BRCA), limiting its therapeutic potential. To shift this balance toward a more favorable antitumor immune response, an indoleamine 2,3‐dioxygenase 1 (IDO1)‐blocking nanozyme specifically designed to potentiate tumor radioimmunotherapy was developed. Using a ZnO–carbon nanoframework, single Cu–N4 catalytic sites were engineered to construct a single‐atom Cu nanozyme (SAzyme) exhibiting dual peroxidase‐ and catalase‐mimicking activities for the delivery of the IDO1 inhibitor 1‐methyl‐tryptophan (1‐MT), resulting in a platform termed CPMR. Phosphorus modification further improved the catalytic performance of the SAzyme. Once internalized by tumor cells, CPMR generates sufficient oxygen to alleviate hypoxia and improve radiosensitivity while simultaneously inducing oxidative stress to promote tumor cell death and trigger immunogenic cell death. These events facilitate the recruitment and activation of tumor‐infiltrating cytotoxic T lymphocytes. The controlled release of 1‐MT inhibits IDO1 activity and reduces L‐tryptophan levels, suppressing regulatory T‐cell function and mitigating the immunosuppressive tumor microenvironment. These mechanisms synergistically improve the efficacy of radiotherapy against BRCA. CPMR represents a promising tumor‐reprogramming strategy capable of eliciting a robust antitumor immune response and significantly strengthening radiotherapeutic outcomes in patients with breast cancer.
SN - 2198-3844
ER -