Photothermal phase-responsive nanocomposites boost cGAS/STING-Driven antitumor immunity via mitochondrial DNA damage

作者：Yuanxiang Yu, Wenjing Li, Yu Shao, Hairui Tian, Tingting Deng, Meili Li, Jiarui Li, X G, Zhenhao Li, Cong Huang, Wei Jiang, Xiaoxiao Luo · 发表于：Materials & Design · 年份：2026 · DOI：10.1016/j.matdes.2026.116629 · 研究领域：interferon and immune responses、Nanoplatforms for cancer theranostics、Cancer Research and Treatments

Activation of the GMP/AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway can sensitize tumors to immunotherapy, yet conventional photothermal therapy (PTT) or photodynamic therapy (PDT) alone rarely generates enough cytosolic double-stranded DNA (dsDNA) to fully engage this axis. Here we develop phase-change lauric-acid nanocomposites (CCL NPs) that co-load photothermal Cu 2-X S nanoparticles and cisplatin. After cellular uptake, near-infrared (NIR) irradiation induces synergistic PTT/PDT, and NIR-II heating melts the lauric-acid shell to trigger on-demand cisplatin release within tumors. The resulting ROS burst together with cisplatin causes extensive mitochondrial DNA damage and dsDNA leakage into the cytosol, leading to robust cGAS/STING activation. In tumor-bearing mice, CCL NPs promote dendritic-cell maturation and antigen cross-presentation, increase cytotoxic T-lymphocyte infiltration, and elicit immunogenic cell death, achieving durable tumor suppression with minimal systemic toxicity. Released copper further contributes via cuproptosis. Overall, CCL NPs integrate controllable chemotherapy with PTT/PDT to amplify innate immune sensing and drive effective antitumor immunity.