Multi-Metallic Nanosheets Reshaping Immunosuppressive Tumor Microenvironment through Augmenting cGAS-STING Innate Activation and Adaptive Immune Responses for Cancer Immunotherapy

被引：3

作者：

Peng, Yuxuan ^{[1
,2
]}

Liang, Shuang ^{[1
,2
]}

Liu, Dan ^{[1
,2
]}

Ma, Kongshuo ^{[1
,2
]}

Yun, Kaiqing ^{[1
,2
]}

Zhou, Mengli ^{[1
,2
]}

Hai, Linna ^{[1
,2
]}

Xu, Mengdi ^{[1
,2
]}

Chen, Yiyang ^{[1
,2
]}

Wang, Zhaohui ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Bioact Subst & Funct Nat Med, Inst Mat Med, Beijing 100050, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing Key Lab Drug Delivery Technol & Novel Form, Beijing 100050, Peoples R China

来源：

ADVANCED SCIENCE | 2024年 / 11卷 / 38期

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

cancer immunotherapy; cGAS-STING signaling pathway; immunosuppressive tumor microenvironment; layered double hydroxides; DNA; THERAPY; PATHWAY;

D O I：

10.1002/advs.202403347

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed for potent anti-tumor immunity by reversing TME. Mn-LDH is synthesized via a one-step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn-LDH effectively releases Mn2+ and Mg2+ upon exposure to TME with high levels of H+ and H2O2, which activates synthase-stimulator of interferon genes pathway and maintains the cytotoxicity of CD8+ T cells respectively, achieving a cascade-like role in innate and adaptive immunity. The locally administered Mn-LDH facilitated a "hot" network consisting of mature dendritic cells, M1-phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn-LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME-modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next-generation cancer immunotherapy. Mn-doped MgAl-LDH is engineered to reprogram immunosuppressive tumor microenvironment through proton neutralization and oxygen generation. The released Mn2+ and Mg2+ initiate a robust cascade immune response, playing a dual role in innate and adaptive immunity by activating the cGAS-STING signaling pathway and sustaining the cytotoxicity of CD8+ T cells, thus effectively inhibiting the growth of primary and distal tumors. image

引用

页数：15