Significance
The combination of cuproptosis and apoptosis that act with different mechanisms holds enormous potential in cancer treatment. Here, copper-coordinated nanoassemblies (CCNAs) based on photosensitizer-chemo prodrugs and checkpoint inhibitors were constructed for mediating cuproptosis-apoptosis and subsequently promoting cancer immunotherapy. CCNAs not only promoted the photodynamic effect and activation of chemotherapy through catalyzing the generation of oxygen but also induced toxic mitochondrial protein aggregation, leading to cell cuproptosis. These synergistic antitumor effects triggered robust immune responses with the aid of immune checkpoint blockade, almost eradicating primary tumors and inhibiting distant tumors by around 83 % without systemic toxicity.
Statement of significance
The combination of cuproptosis and apoptosis that act with different mechanisms holds enormous potential in cancer treatment. Here, copper-coordinated nanoassemblies (CCNAs) based on photosensitizer-chemo prodrugs and checkpoint inhibitors were constructed for mediating cuproptosis-apoptosis and subsequently promoting cancer immunotherapy. CCNAs not only promoted the photodynamic effect and activation of chemotherapy through catalyzing the generation of oxygen but also induced toxic mitochondrial protein aggregation, leading to cell cuproptosis. These synergistic antitumor effects triggered robust immune responses with the aid of immune checkpoint blockade, almost eradicating primary tumors and inhibiting distant tumors by around 83 % without systemic toxicity.