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

Significance 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. Approach 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. Results 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. Conclusions 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.