作者：

Shuai Zhang, Chunjie Wang, Yujie Zhu, Juxin Gao, Yifan Yan, Minming Chen, Xiaoying Yan, Zhuang Liu*, and Liangzhu Feng*

单位：

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren’ai Road, Suzhou, Jiangsu 215123, P. R. China.

摘要：

The radiotherapy-induced release of DNA fragments can stimulate the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway to prime antitumor immunity, but this pathway is expected to be less potent because of the inefficient cytosolic delivery of negatively charged DNA fragments. In this study, manganese-coordinated chitosan (CS-Mn) microparticles with selective DNA-capturing capacity are concisely prepared via a coordination-directed one-pot synthesis process to potentiate the immunogenicity of radiotherapy. The obtained CS-Mn microparticles that undergo rapid disassembly under physiological conditions can selectively bind with DNA to form positively charged DNA-CS assemblies because of the strong electrostatic interaction between linear chitosan and DNA molecules. They thus enable efficient cytosolic delivery of DNA in the presence of serum to cooperate with Mn²⁺to activate the cGAS-STING pathway in dendritic cells. Upon intratumoral injection, the CS-Mn microparticles markedly enhance the efficacy of radiotherapy against both irradiated and distal tumors in different tumor models via collectively promoting tumor-infiltrating CD8⁺T-cell stemness and the activation of innate immunity. The radiosensitization effect of CS-Mn microparticles can be further augmented by concurrently applying anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. This work highlights an ingenious strategy to prepare Trojan horse-like DNA-capturing microparticles as cGAS-STING-activating radiosensitizers for effective radioimmunotherapy

影响因子：

27.4

分区情况：

一区

链接：

https://doi.org/10.1002/adma.202418583