Tumor Metabolism Aiming Cu2–xS Nanoagents Mediate Photothermal-Derived Cuproptosis and Immune Activation

S (MACuS) through a glucose-mediated biomineralization approach. MACuS nanoagents can be specifically targeted to tumors via the glucose transport receptor 1, and we found that NIR-II irradiation can not only result in direct hyperthermia ablation of tumor cells but also facilitate efficient cuproptosis and enhance reactive oxygen species-induced cytotoxicity in tumor cells. As a result, the triple effect of MACuS treatment induced immunogenic cell death, which triggered systemic antitumor immune responses and demonstrated potent efficacy in inhibiting growth, metastasis, and recurrence in mouse and rabbit breast cancer models. The precise intracellular delivery and redox control of copper provided by MACuS hold great potential for the development of highly efficient cuproptosis-based tumor therapies with minimal off-target effects.