A Copper-Based Photothermal-Responsive Nanoplatform Reprograms Tumor Immunogenicity via Self-Amplified Cuproptosis for Synergistic Cancer Therapy

Studies show that intracellular accumulation of copper ions causes cuproptosis, potentially enhancing anticancer immunity. However, the induction of cuproptosis inevitably faces challenges due to low intracellular copper deliver efficiency and collateral damage to normal tissues. This paper presents a self-amplified cuproptosis nanoplatform (CEL NP) composed of Cu2-XS hollow nanospheres (HNSs), elesclomol (ES), and phase-change material lauric acid (LA). Under NIR-II laser irradiation, the photothermal energy generated by Cu2-XS HNSs melts LA, facilitating the precise release of ES and copper ions within the tumor microenvironment. Notably, ES can traverse the cell membrane and form ES-Cu(II) complexes, thereby enhancing copper delivery within tumor cells. Excess Cu(II) also reacts with endogenous glutathione, reducing its inhibitory effect on cuproptosis. Ultimately, this amplified cuproptosis effect can activate immunogenic cell death, eliciting a robust immune response and promoting tumor suppression. The CEL NP-mediated release of ES and copper ions offers a novel approach for anticancer therapy through cuproptosis induction.