Dual metabolism-disrupted nanoparticles for reprogramming the immune microenvironment to potentiate cuproptosis immunotherapy

copper coordination-driven assembly of a glycolysis inhibitor and an indoleamine-pyrrole 2,3-dioxygenase 1 inhibitor. After intravenous administration, LN NPs effectively accumulated at tumor sites to enhance the bioavailability of therapeutic agents. They simultaneously disrupted glycolysis and amino acid metabolism, resulting in a reduction in the levels of inhibitory metabolites and alleviating tumor immunosuppression. Furthermore, the inhibition of glycolysis generating reactive oxygen species, and copper-triggered cuproptosis synergistically induced potent immunogenic cell death. Subsequently, LN NPs elicited a robust cascade of immunological responses that effectively inhibited tumor growth and metastasis. Overall, this study offered a promising paradigm for tumor treatment via the synergistic dual metabolic modulation and cuproptosis immunotherapy.