Blocking Metallothionein‑2\nExpression by Copper-Doped\nCarbon Dots Induces Cellular Antioxidant System Collapse for Antitumor\nTherapy

The insufficient antioxidant reserves in tumor cells\nplay a critical\nrole in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2\n(MT-2), an intracellular cysteine-rich protein renowned for its potent\nantioxidant properties, is intricately involved in tumor development\nand correlates with a poor prognosis. Consequently, MT-2 emerges as\na promising target for tumor therapy. Herein, we present the development\nof copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise\nthe delicate antioxidant reserves in tumor cells. These Cu-CDs with\nhigh tumor accumulation and prolonged body retention can effectively\nsuppress tumor growth by inducing oxidative stress. Transcriptome\nsequencing unveils a significant decrease in MT-2 expression within\nthe <i>in vivo</i> tumor samples. Further mechanical investigations\ndemonstrate that the antitumor effect of Cu-CDs is intricately linked\nto apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression\nand the collapse of the antioxidant system. The robust antitumor efficacy\nof Cu-CDs provides invaluable insights into developing MT-2-targeted\nnanomedicine for cancer therapies.