铜中毒依赖于铜超载，为癌症治疗提供了新的机会。铜基纳米材料在铜的细胞内输送方面表现出优异的优势。然而，铜纳米材料将铜离子转运到癌细胞中的生物学过程仍不清楚。在这项研究中，我们在单细胞水平上追踪了铜纳米线（CuNW）和铜纳米粒子（CuNP）的铜离子释放过程。发现长度为 5 μm 的 CuNW 和 CuNP 被癌细胞完全内化。有趣的是，CuNWs 逃离了内溶酶体系统，而 CuNPs 主要被困在溶酶体中。 CuNW 的这种特定细胞内分布导致细胞质铜离子过载，直接损害线粒体并诱导二氢硫辛酰胺 S-乙酰转移酶 (DLAT) 蛋白聚集。通过这些过量的铜离子，CuNWs 比 CuNPs 更有效地引发铜凋亡，进一步增加细胞死亡。因此，CuNW 在传递 Cu 离子方面比 CuNP 更有效，为设计用于癌症治疗的基于铜凋亡的功能纳米材料提供了新的视角。

Cuproptosis, dependent on Cu overload, presents novel opportunities for cancer therapy. Cu-based nanomaterials have shown excellent advantages for the intracellular delivery of Cu. However, the biological process of Cu nanomaterials transporting Cu ions into cancer cells remains unclear. In this study, we tracked the Cu ion release process of copper nanowires (CuNWs) and copper nanoparticles (CuNPs) at the single-cell level. CuNWs with 5-μm length and CuNPs were found to be completely internalized by cancer cells. Interestingly, CuNWs escaped from the endolysosomal system, whereas CuNPs were mainly trapped in the lysosomes. This specific intracellular distribution of CuNWs led to cytoplasmic Cu ion overload, directly damaging mitochondria and inducing dihydrolipoamide S-acetyltransferase (DLAT) protein aggregation. Through these excessive Cu ions, CuNWs triggered more efficient cuproptosis than CuNPs to further increase cell death. Thus, CuNWs are more effective in delivering Cu ions than CuNPs, providing a novel perspective for designing cuproptosis-based functional nanomaterials for cancer therapy.