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- Title
Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation.
- Authors
Wang, Kaiyuan; Li, Yang; Wang, Xia; Zhang, Zhijun; Cao, Liping; Fan, Xiaoyuan; Wan, Bin; Liu, Fengxiang; Zhang, Xuanbo; He, Zhonggui; Zhou, Yingtang; Wang, Dong; Sun, Jin; Chen, Xiaoyuan
- 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. Gas-based therapy is an emerging therapeutic option for cancer treatment. Here the authors design a virus-mimicking hollow mesoporous tetrasulfide-doped organosilica for co-encapsulation of an aggregation-induced emission (AIE)-active luminogen and manganese carbonyl to fabricate a STING activating gas nano-adjuvant for photo-immunotherapy, promoting anti-tumor immune response in preclinical models.
- Subjects
HYDROGEN sulfide; TRIPLE-negative breast cancer; TYPE I interferons; CARBOXYHEMOGLOBIN; MITOCHONDRIAL DNA
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-38601-7