Tumor Microenvironment Responsive Copper-Doped Carbon Dots for Synergistic Chemotherapy and Cuproptosis in Laryngeal Cancer

Laryngeal squamous cell carcinoma (LSCC) has a poor prognosis because it is often diagnosed late and chemotherapy causes substantial side effects. To improve efficacy and reduce toxicity, we developed a tumor microenvironment-responsive nanoplatform, 5-fluorouracil-loaded copper-doped carbon dots (5-Fu@CuCDs). The nanocomposite was synthesized by a one-step hydrothermal method, showed a uniform spherical morphology of about 15.7 nm, and achieved a drug loading rate of about 30%. Structural analyses confirmed successful copper doping and stable drug incorporation. Under weakly acidic tumor microenvironment conditions, the nanoplatform catalyzed hydroxyl radical generation from hydrogen peroxide and depleted intracellular glutathione, thereby enhancing oxidative stress. Density functional theory calculations further supported its high peroxidase-like catalytic activity. In vitro, the nanoplatform was efficiently taken up by laryngeal cancer cells, promoted copper accumulation and oxidative stress, and showed stronger antitumor activity than free 5-fluorouracil or copper-doped carbon dots, while maintaining good biocompatibility.