铜中毒是一种新兴的细胞死亡形式，依赖于将铜离子靶向递送至硫酰化三羧酸循环蛋白。然而，与铜凋亡相关的一个主要挑战是它有可能不加区别地杀死正常细胞和肿瘤细胞。因此，制定铜的精确细胞内递送和氧化还原控制策略以创建有效的基于铜凋亡的肿瘤疗法至关重要。我们通过葡萄糖介导的生物矿化方法引入了一类称为代谢目标 Cu2-xS (MACuS) 的纳米制剂。 MACuS纳米制剂可以通过葡萄糖转运受体1特异性靶向肿瘤，我们发现NIR-II照射不仅可以导致肿瘤细胞直接热消融，还可以促进有效的铜凋亡并增强活性氧诱导的肿瘤细胞细胞毒性。因此，MACuS 治疗的三重效应诱导免疫原性细胞死亡，从而引发全身抗肿瘤免疫反应，并在小鼠和兔乳腺癌模型中显示出抑制生长、转移和复发的有效功效。 MACuS 提供的铜的精确细胞内递送和氧化还原控制对于开发高效的基于铜凋亡的肿瘤疗法具有巨大的潜力，并且脱靶效应最小。

Cuproptosis is an emerging form of cell death that relies on the targeted delivery of copper ions to lipoylated tricarboxylic acid cycle proteins. However, a major challenge associated with cuproptosis is its potential to kill both normal and tumor cells without discrimination. Therefore, it is crucial to develop strategies for precise intracellular delivery and redox control of copper to create effective cuproptosis-based tumor therapies. We have introduced a class of nanoagents called metabolism aiming Cu2-xS (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.