Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation.
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| Abstract |
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 (H2S). Upon near-infrared laser irradiation, the AIEgen-mediated phototherapy triggers the burst of carbon monoxide (CO)/Mn2+. Both H2S 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, Mn2+ 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.
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| Authors | Kaiyuan Wang, Yang Li, Xia Wang, Zhijun Zhang, Liping Cao, Xiaoyuan Fan, Bin Wan, Fengxiang Liu, Xuanbo Zhang, Zhonggui He, Yingtang Zhou, Dong Wang, Jin Sun, Xiaoyuan Chen |
| Journal | Nature communications (Nat Commun) Vol. 14 Issue 1 Pg. 2950 (05 23 2023) ISSN: 2041-1723 [Electronic] England |
| PMID | 37221157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2023. The Author(s). |
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