程亮教授课题组在ACS Nano上发表论文

题目：

Zinc−Nickel Bimetallic Hydroxide Nanosheets Activate the Paraptosis−Pyroptosis Positive Feedback Cycle for Enhanced Tumor Immunotherapy

作者：

Youdong Chen¹, Yujie Lu¹, Huali Lei¹, Lin Liu¹, Xianmin Li¹, Yuqi Yang¹, Shumin Sun¹, Qiao Yu¹, Li Wang¹, Jie Wu^1,2, Jingrui Li¹, Guanghui Hou¹* and Liang Cheng^1,2*

单位：

¹Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.

²Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa, Macau SAR 999078, China.

摘要：

Immunotherapy holds significant promise for cancer treatment. However, the highly immunosuppressive nature of solid tumors limits its effectiveness. Herein, we developed bioactive zinc−nickel hydroxide (ZnNi(OH)₄) nano-sheets (NSs) that can effectively initiate the paraptosis−pyroptosis positive feedback cycle through synergistic ionic effect, thereby mitigating the immunosuppression of solid tumors and enhancing the efficacy of immunotherapy. The acid-sensitive ZnNi(OH)₄ NSs releases Ni²⁺ and Zn²⁺ in the weakly acidic tumor microenvironment. The released Ni²⁺ alleviated pyroptosis inhibition by inducing paraptosis and inhibiting autophagic flux. Concurrently, Ni²⁺ triggered release of endogenous Zn²⁺ within the cell through a coordination competition mechanism, further amplifying zinc overload-mediated pyroptosis. Interestingly, pyroptosis-associated oxidative stress and endoplasmic reticulum stress further promote Ni²⁺-mediated paraptosis, forming a positive feedback loop between pyroptosis and paraptosis. This process not only effectively kills tumor cells but also stimulates a strong inflammatory response, enhancing the antitumor immune response and immunotherapy efficacy. Overall, this study proposes an effective paraptosis−pyroptosis induction strategy based on metal ions and demonstrates the effectiveness of the positive feedback loop of paraptosis−pyroptosis in potentiating immunotherapy.

影响因子：

15.8

分区情况：

一区

链接：

https://doi.org/10.1021/acsnano.4c10378