Intervention in the Crosstalk between the cGAS-STING Pathway and Autophagy Using an Oligonucleotide-Based Bioorthogonal Platform for Amplifying Immunotherapy
文献类型： 外文期刊
作者： Xu, Guoshi 1 ; Shu, Yinuo 1 ; Jiang, Minhao 1 ; Zhang, Yanjie 1 ; Zhu, Jiawei 1 ; Peng, Yinghua 4 ; Pu, Fang 1 ; Ren, Jinsong 1 ; Qu, Xiaogang 1 ;
作者机构： 1.Chinese Acad Sci, State Key Lab Rare Earth Resource Utilizat, Changchun Inst Appl Chem, Changchun 130022, Jilin, Peoples R China
2.Chinese Acad Sci, Changchun Inst Appl Chem, Lab Chem Biol, Changchun 130022, Jilin, Peoples R China
3.Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China
4.Chinese Acad Agr Sci, Inst Special Anim & Plant Sci, Changchun 130112, Jilin, Peoples R China
关键词： crosstalk; cGAS-STING; autophagy; oligonucleotide; bioorthogonal chemistry; immunotherapy
期刊名称：NANO LETTERS （ 影响因子：9.1； 五年影响因子：9.9 ）
ISSN： 1530-6984
年卷期： 2025 年 25 卷 24 期
页码：
收录情况： SCI
摘要： The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway can respond to double-stranded DNA (dsDNA) to mediate innate immunity. However, activation of the cGAS/STING pathway initiates autophagy, which typically plays a negative regulatory role in the cGAS-STING pathway, largely attenuating the efficacy of antitumor immunity. Herein, we construct an oligonucleotide-based bioorthogonal platform to intervene in the crosstalk between the cGAS-STING pathway and autophagy, thereby achieving enhanced immunotherapy. In the platform, a dsDNA segment conjugated with unpaired guanosines serves as an agonist for the cGAS-STING pathway. The i-motif acts as a template for synthesizing palladium nanoparticles, which catalyze the synthesis of autophagy inhibitor and also function as carriers of oligonucleotides. Furthermore, the platform includes an aptamer for targeted delivery to cancer cells. In cancer cells, the platform activates the cGAS-STING pathway and disrupts autophagy, enhancing the anticancer immunity. This study provides a promising strategy to improve outcomes in tumor immunotherapy.
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