• MCPG nanozymes with sulfur vacancies enable cascade catalytic reactions that continuously replenish H2O2 and O2, overcoming tumor hypoxia and GSH-mediated resistance.
• Mn doping induces structural reconstruction and enhances catalytic activity of sulfur vacancy sites, as confirmed by density functional theory calculations.
• Under 1064 nm laser, MCPG exhibits photothermoelectric catalysis, generating ROS and disrupting redox homeostasis to trigger cuproptosis, ferroptosis, and apoptosis.
• Multimodal imaging-guided synergistic therapy not only eradicates primary tumors but also elicits antitumor immune responses to inhibit metastasis.