Copper-Based Nanoscale Coordination Polymers Augmented Tumor Radioimmunotherapy for Immunogenic Cell Death Induction and T-Cell Infiltration

Insufficient T-cell infiltration seriously hinders the efficacy of tumor immunotherapy. Induction of immunogenic cell death (ICD) is a potentially feasible approach to increase T-cell infiltration. Since ionizing radiation can only induce low-level ICD, this study constructs Cu-based nanoscale coordination polymers (Cu-NCPs) with mixed-valence (Cu+/Cu2+), which can simultaneously and independently induce the generation of Cu+-triggered hydroxyl radicals and Cu2+-triggered GSH elimination, to synergize with radiation therapy for potent ICD induction. Markedly, this synergetic therapy remarkably enhances dendritic cell maturation and promotes antitumor CD8(+) T-cell infiltration, thereby potentiating the development of checkpoint blockade immunotherapies against primary and metastatic tumors.