Bimetallic nanoplatform inducing robust cuproptosis to enhance tumor immunotherapy via immunogenic activation and tumor microenvironment reprogramming

作者：Meng Dang, Qiang Li, Xuzhi Shi, Ao He, Xiaoye Li, Zhuo Dai, Jiaxin Rui, Weiqing Ning, Zhaogang Teng, Heng Dong, Yongbin Mou · 发表于：Chemical Engineering Journal · 年份：2025 · DOI：10.1016/j.cej.2025.164958 · 被引用次数：5 · 研究领域：Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery、Phagocytosis and Immune Regulation

Cuproptosis, a novel copper-dependent cell death mechanism distinct from apoptosis, offers potential breakthroughs in overcoming resistance to conventional tumor therapies. Current challenges include the safe delivery of adequate copper concentrations, selective targeting to tumor cells, potential resistance development, and overcoming immunosuppressive tumor environments. We introduce a synergistic approach using an near-infrared (NIR)-II activatable bimetallic nanoplatform, termed APDC, which integrates cuproptosis with immunotherapy. In this design, copper ions (Cu 2+ ) and disulfiram (DSF) are sequestered within the nanoplatforms by lauric acid (LA), ensuring stability until NIR-II irradiation. Upon NIR-II irradiation, APDC's photothermal properties melt LA, releasing Cu 2+ and DSF which react to form cytotoxic bis(diethyldithiocarbamate)copper complex (CuET) and cuprous ions (Cu + ), facilitating effective cuproptosis and apoptosis. In vivo studies reveal that APDC under NIR-II light not only significantly curtails tumor growth compared to monotherapies but also triggers strong antigen-presentation response and immunosuppression reprogramming. This effects includes dendritic cell maturation, heightened infiltration of cytotoxic T lymphocytes, and activation of memory T cells, and effectively converting immunologically “cold” tumors into responsive “hot” tumors, collectively inhibiting both primary and distant tumors in squamous cell carcinoma models. Our findings show th...