Hybrid Cell Membrane-FunctionalizedNanoagents SynergisticallyEnhance Cuproptosis-Mediated Immunotherapy by Dual Modulation of GlycolyticMetabolism and Tumor Microenvironments

作者：Qiang Li, Meng Dang, Aijun He, Xiaoye Li, Meng Ding, Zhuo Dai, Yu Zhang, Weijun Xiu, Siyu Wang, Zhusheng Huang, Yongbin Mou, Lianhui Wang, Heng Dong · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.5c10671 · 被引用次数：18 · 研究领域：Nanoplatforms for cancer theranostics、Immune cells in cancer、Phagocytosis and Immune Regulation

Glycolytic activity of cancer cells not only reduces their vulnerability to cuproptosis but also heightens the immunosuppressive state of the tumor microenvironment (TME). Our study introduces a nanoplatform called dual-remodeling cuproptosis-inducing agent with hybrid cell membrane coating (DREAM), which is crafted to simultaneously modify the metabolic and immunological landscapes of the TME to enhance cuproptosis-driven immunotherapy. This platform exploits cancer-cell-derived membranes for homologous targeting, enhancing tumor specificity, intratumoral penetration, and intracellular copper delivery. DREAM's disruption of glycolysis intensifies the copper overload, triggering cuproptosis in cancer cells. Additionally, it alleviates immunosuppression and bolsters immune responses facilitated by the immunogenic cell death from cuproptosis, further potentiated by the immunostimulatory effect of M1 macrophage membranes. The outcome is a pronounced efficacy in curbing tumor growth and distant metastasis in squamous cell carcinoma and also in suppressing melanoma proliferation and lung metastasis. This research underscores the vital interaction among inhibiting glycolysis, enhancing sensitivity to cuproptosis, and activating immune responses, thereby paving a feasible and integrated pathway in cancer immunotherapy.