题目：

Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment

作者：

Lin Liu^1#, Huali Lei^2#, Guanghui Hou^2*, Lin Zhang¹, Youdong Chen², Yujie Lu², Zifan Pei², Jun Ge¹, Jie Wu², Jinhua Zhou¹*, and Liang Cheng²*

单位：

¹Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

²Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.

摘要：

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness of immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectivey enhance the antitumor immune response of the cervical cancer through gas-amplified metalloimmunotherapy with dual activation of pyroptosis and STING pathway. The bioactive MCSP exhibited the ability to rapidly release Ca²⁺, Mn²⁺, and H₂S in response to the tumor microenvironment. H₂S disrupted the calcium buffer system of cancer cells by interfering with the oxidative phosphorylation pathway, leading to calcium overload-triggered pyroptosis. On the other hand, H₂S-mediated mitochondrial dysfunction further promoted the release of mitochondrial DNA (mtDNA), enhancing the activation effect of Mn²⁺on the cGAS-STING signaling axis and thereby activating immunosuppressed dendritic cells. The released H₂S acted as an important synergist between Mn²⁺and Ca²⁺by modulating dual signaling mechanisms to bridge innate and adaptive immune responses. The combination of MCSP NPs and PD-1 immunotherapy achieved synergistic antitumor effects and effectively inhibited tumor growth. This study reveals the potential collaboration between H₂S gas therapy and metalloimmunotherapy and provides an idea for the design of nanoimmunomodulators for rational regulation of the immunosuppressive tumor microenvironment.

影响因子：

15.8

分区情况：

一区

链接：

https://doi.org/10.1021/acsnano.4c00017

责任编辑：郭佳