Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation.

Autor: Wang K; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, P. R. China.; Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, 119074, Singapore., Li Y; Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China.; Department of Translational Medicine & Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare-Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, 361021, P. R. China., Wang X; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China., Zhang Z; Center for AIE Research, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China., Cao L; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, P. R. China., Fan X; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, P. R. China., Wan B; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, P. R. China., Liu F; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, P. R. China., Zhang X; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, P. R. China.; Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, 119074, Singapore., He Z; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, P. R. China., Zhou Y; National Engineering Research Center for Marine Aquaculture, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, Zhejiang Province, 316004, China. zhouyingtang@zjou.edu.cn., Wang D; Center for AIE Research, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China. wangd@szu.edu.cn., Sun J; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, P. R. China. sunjin@syphu.edu.cn., Chen X; Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, 119074, Singapore. chen.shawn@nus.edu.sg.; Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore. chen.shawn@nus.edu.sg.; Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore. chen.shawn@nus.edu.sg.; Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore. chen.shawn@nus.edu.sg.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 23; Vol. 14 (1), pp. 2950. Date of Electronic Publication: 2023 May 23.
DOI: 10.1038/s41467-023-38601-7
Abstrakt: The immunologically "cold" microenvironment of triple negative breast cancer results in resistance to current immunotherapy. Here, we reveal the immunoadjuvant property of gas therapy with cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation to augment aggregation-induced emission (AIE)-active luminogen (AIEgen)-based photoimmunotherapy. A virus-mimicking hollow mesoporous tetrasulfide-doped organosilica is developed for co-encapsulation of AIEgen and manganese carbonyl to fabricate gas nanoadjuvant. As tetra-sulfide bonds are responsive to intratumoral glutathione, the gas nanoadjuvant achieves tumor-specific drug release, promotes photodynamic therapy, and produces hydrogen sulfide (H 2 S). Upon near-infrared laser irradiation, the AIEgen-mediated phototherapy triggers the burst of carbon monoxide (CO)/Mn 2+ . Both H 2 S and CO can destroy mitochondrial integrity to induce leakage of mitochondrial DNA into the cytoplasm, serving as gas immunoadjuvants to activate cGAS-STING pathway. Meanwhile, Mn 2+ can sensitize cGAS to augment STING-mediated type I interferon production. Consequently, the gas nanoadjuvant potentiates photoimmunotherapy of poorly immunogenic breast tumors in female mice.
(© 2023. The Author(s).)
Databáze: MEDLINE
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