Amplifying STING Activation and Alleviating Immunosuppression through a Mn 2+-Based Metal-Organic Framework Nanosystem for Synergistic Cancer Therapy

作者全名：Fang, Mingxiao; Zheng, Jun; Wang, Jingxue; Zheng, Chenpeng; Leng, Xiaojing; Wen, E.; Li, Pan; Ran, Haitao; Zhang, Liang; Wang, Zhigang

作者地址：[Fang, Mingxiao; Zheng, Jun; Wang, Jingxue; Leng, Xiaojing; Wen, E.; Li, Pan; Ran, Haitao; Zhang, Liang; Wang, Zhigang] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, State Key Lab Ultrasound Med & Engn, Chongqing 400010, Peoples R China; [Zheng, Chenpeng] Chongqing Univ Cent Hosp, Chongqing Emergency Med Ctr, Chongqing 400014, Peoples R China; [Zhang, Liang] Chongqing Med Univ, Affiliated Hosp 1, Ultrasound Dept, Chongqing 400042, Peoples R China

通信作者：Wen, E; Zhang, L; Wang, ZG (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, State Key Lab Ultrasound Med & Engn, Chongqing 400010, Peoples R China.; Zhang, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Ultrasound Dept, Chongqing 400042, Peoples R China.

来源：BIOMATERIALS RESEARCH

ESI学科分类：　

WOS号：WOS:001223707500001

JCR分区：Q1

影响因子：8.1

年份：2024

卷号：28

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：The field of immunotherapy, particularly immune checkpoint blockade (ICB), holds immense potential in mitigating the progression of cancer. However, the challenges of insufficient tumor antigen production and the immunosuppressive state in the tumor microenvironment substantially impede patients from deriving benefits. In this research, we present a tumor-microenvironment-modulation manganesebased nanosystem, PEG-MnMOF@PTX, aiming to improve the responsiveness of ICB. Under acidic conditions, the released Mn 2 + accomplishes multiple objectives. It generates toxic hydroxyl radicals (center dot OH), together with the released paclitaxel (PTX), inducing immunogenic cell death of tumor cells and normalizing tumor blood vessels. Concurrently, it facilitates the in situ generation of oxygen (O 2 ) from hydrogen peroxide (H 2 O 2 ), ameliorating the microenvironmental immunosuppression and increasing the efficacy of immunotherapy. In addition, this study demonstrates that PEG-MnMOF@PTX can promote the maturation of dendritic cells and augment the infiltration of cytotoxic T lymphocytes through activation of the cyclic guanosine 5 '-monophosphate-adenosine 5 '-monophosphate synthase (cGAS) and interferon gene stimulator (STING) pathways, namely cGAS-STING pathways, thereby heightening the sensitivity to ICB immunotherapy. The findings of this study present a novel paradigm for the progress in cancer immunotherapy.

基金机构：National Natural Science Foundation of China [82202175, 82172092]; Postdoctoral Fellowship Program of CPSF [GZC20233358]; Key Project of Application Development Plan of Chongqing [cstc2019jscx-dxwtBX0004]; China Postdoctoral Science Foundation [2023MD744164]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0093]

基金资助正文：Funding: This work was supported by the National Natural Science Foundation of China (grant nos. 82202175 and 82172092) , Postdoctoral Fellowship Program of CPSF (GZC20233358) , Key Project of Application Development Plan of Chongqing (grant no. cstc2019jscx-dxwtBX0004) , China Postdoctoral Science Foundation (2023MD744164) , and Natural Science Foundation of Chongqing (grant no. CSTB2022NSCQ-MSX0093) .