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.

三阴性乳腺癌的免疫“冷”微环境导致对当前免疫疗法的抵抗。在这里，我们揭示了气体疗法与干扰素基因的环状 GMP-AMP 合酶刺激物 (cGAS-STING) 通路激活的免疫辅助特性，以增强基于聚集诱导发光 (AIE)-活性发光原 (AIEgen) 的光免疫疗法。开发了一种模拟病毒的中空介孔四硫化物掺杂有机二氧化硅，用于共包封 AIEgen 和羰基锰以制备气体纳米佐剂。由于四硫键响应瘤内谷胱甘肽，气体纳米佐剂实现肿瘤特异性药物释放，促进光动力治疗，产生硫化氢（H ₂S). 在近红外激光照射下，AIEgen 介导的光疗会触发一氧化碳 (CO)/Mn ²⁺的爆发。H ₂ S和CO均可破坏线粒体完整性，诱导线粒体DNA渗漏到细胞质中，作为气体免疫佐剂激活cGAS-STING通路。同时，Mn ²⁺可以使 cGAS 敏感以增加 STING 介导的 I 型干扰素的产生。因此，气体纳米佐剂增强了雌性小鼠免疫原性较差的乳腺肿瘤的光免疫疗法。