作者：

Zifan Pe^1#i, Yifan Yin^2,3#, Nailin Yang^1#, Shumin Sun¹, Nan Jiang⁴, Fangyi Yu¹, Xiaofen Zhang¹, Jihu Nie¹, Youdong Chen¹, Longxiao Li¹, Jie Wu¹, Fei Gong¹, Minming Chen¹, Wei Liu², and Liang Cheng¹*

单位：

¹Institute of Functional Nano and Soft Materials (FUNSOM), Biomedical-Basic Research-Center (BBRC) of Jiangsu Province, Soochow University, 199 Ren’Ai Rd., Suzhou 215123, China

²Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201112, China

³Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China

⁴Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China

摘要：

Clinical evidence has suggested that persistent STAT3 activation and alteration in lipid metabolism correlate with pathological progression in patients with breast cancer, driving resistance to chemotherapy. Herein, we show that H₂S, an endogenous gas signaling molecule, sensitizes breast cancer to chemotherapy by suppressing STAT3 signaling-mediated lipid metabolism and improves tumor immunogenicity. Moreover, we further identify Ni²⁺ as immune agonist for potent metalloimmunotherapy. The construction of an activable nanoplatform enables the controllable delivery of metal ions and H₂S gas, which triggers pyroptosis and mobilizes multiple immune cells to elicit systemic anti-tumor immunity in combination with chemotherapy. Moreover, the synergy with αPD-1 inhibits the progression of both primary and metastatic tumors. Our work highlights the potential of bioactive gas transmitters and nutrient metal ions for reversing the dual dilemmas of chemoresistance and low immunogenicity in breast cancer and thus provides a nanosensitization strategy to synergize with multiple clinical treatment modalities.

影响因子：

10.6

分区情况：

一区

链接：

https://doi.org/10.1016/j.xcrm.2026.102844