Multifunctional Thermoelectric Nanocatalysts for Synergistic Uveal Melanoma Treatment by Specific Cuproptosis and Pyroptosis

Abstract Uveal melanoma (UM) is a highly aggressive ocular malignancy associated with a poor prognosis and significant resistance to conventional therapies, including surgical resection, chemotherapy, and radiotherapy, which are often limited by their efficacy and adverse side effects. Energy‐conversion‐based nanodynamic therapy, which facilitates the generation of reactive oxygen species (ROS), has emerged as a promising approach for cancer treatment. Here, the development of high‐performance multifunctional thermoelectric nanocatalysts, specifically Cu 5 FeS 3.6 Se 0.4 nanoparticles, optimized for the effective synergistic treatment of UM is reported. These nanoparticles exhibit remarkable photothermal, thermoelectric, and chemodynamic properties that enhance therapeutic efficacy. Under near‐infrared light irradiation, Cu 5 FeS 3.6 Se 0.4 nanoparticles generate localized hyperthermia, which not only induces direct tumor cell ablation but also produces thermoelectric potentials that facilitate ROS generation. Additionally, the hyperthermia induced by the photothermal effects of these nanoparticles accelerates a Fenton‐like reaction, leading to the formation of highly reactive hydroxyl radicals for chemodynamic therapy. The resultant ROS induce oxidative stress within tumor cells, promoting mechanisms such as cuproptosis and pyroptosis. The integration of photothermal effects, thermoelectric potentials, and chemodynamic therapy within a single nanoplatform represents an efficient strategy for UM treatment, addressing the shortcomings of traditional therapies and offering a highly effective means of managing this aggressive cancer.