Highly copper ion mobile bornite nanoparticles enable efficient photothermoelectric catalysis therapy synergized by cuproptosis/ferroptosis

Evading programmed cell death is a major obstacle in tumor treatment. Photothermoelectric catalytic (PTEC) therapy shows promise, but optimizing its effect is challenging due to complex thermoelectric parameter interdependencies. Cuproptosis and ferroptosis, metal-dependent cell death pathways, have potential in tumor treatment when synergistically activated. High-cubic bornite nanoparticles with phonon-liquid electron-crystal properties were developed and surface-modified with anti-glypican-3 antibodies. Solvothermal methods were used for synthesis, and various characterization techniques, in vitro and in vivo experiments, and DFT calculations were employed. CFS nanoparticles exhibited excellent photothermoelectric performance, generating ROS. CFS@GPC3 NPs effectively targeted hepatocellular carcinoma cells, activated cuproptosis and ferroptosis, and inhibited tumor growth both in vitro and in vivo. Transcriptome analysis verified the energy conversion-mediated therapeutic strategy. The designed CFS@GPC3 NPs enable efficient PTEC-mediated tumor treatment by integrating photothermal and thermoelectric processes and synergizing cuproptosis and ferroptosis, providing a new paradigm for PTEC-related nanomedicine design.