FA/HCQ-Functionalized Ag-Doped Quantum Dots: A Triple-Modal Nanoplatform for Mild-Temperature Photothermal Cancer Therapy

To improve the trade-off between efficacy and safety in photothermal therapy (PTT), we report folic acid (FA)/hydroxychloroquine (HCQ)-dual-functionalized Ag-doped CuInSe2/ZnS quantum dots (ACFQ QDs) for mild PTT (MPTT). The ACFQ QDs achieve a photothermal conversion efficiency of 42.6% under 808 nm laser, enabling tumor ablation at 43 °C. HCQ inhibits autophagic self-repair of cancer cells under sublethal thermal stress, while FA targets folate receptor-overexpressing tumors. In vitro, ACFQ QDs induce significant apoptosis, suppress clonogenicity and invasion, and generate reactive oxygen species (ROS) for synergistic photodynamic therapy (PDT). Studies on nude mice have shown a tumor suppression rate of over 80%, with negligible systemic toxicity and normal tissue damage. The dual-ligand strategy overcomes limitations of conventional QDs, combining photothermal, photodynamic, and autophagy-inhibiting effects for a translatable cancer therapy paradigm.