STING Activation by Photo-immunogenic Nanophotocages for Synergistic Photoimmunotherapy of Cold Tumor
Lili Yao1, Sixin Li1, Xiaohe Zhang1, Youkang Zhai1, Jiaping Shen1, Chao Deng1, Wenhai Lin(林文孩)1*, Shengliang Li(李盛亮)2*, Zhiyuan Zhong(钟志远)1,2*
1Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
2College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
J. Am. Chem. Soc., 2026, 148, 29710-29722
Abstract: Reversing the immunosuppressive tumor microenvironment (ITME) is a crucial obstacle in the immunotherapy of cold tumor. The STING signaling pathway has shown promise in overcoming the ITME issue. However, reversing ITME via precise activation of the STING signaling pathway remains a significant challenge. In this work, photoresponsive nanophotocages with photoimmunogenic performance were developed for ITME-reversed synergistic photoimmunotherapy of cold tumor. In the photocage design, photoresponsive boron dipyrromethene (BODIPY) was used to link a STING agonist (DMXAA) and then prepared into water-dispersible nanoparticles. The iodinated nanophotocage showed the best photoreaction efficiency and spatiotemporal controllability among the four nanophotocages. Under light irradiation, the iodinated nanophotocages precisely released the STING agonist and triggered immunogenic cell death (ICD) via the photodynamic therapy (PDT) effect, by which the ITME was reversed to enhance the immune checkpoint inhibitor (aCTLA4) immunotherapy. The robust immune response not only achieved primary tumor eradication in 80% of the mice but also significantly inhibited the distant tumor. This work offers a photoimmunogenic photocage for light-controlled STING activation for ITME-reversed cancer photoimmunotherapy.
Article information:https://doi.org/10.1021/jacs.6c01388