DNA Adjuvant Hydrogel‐Optimized Enzymatic Cascade Reaction for Tumor Chemodynamic‐Immunotherapy

Abstract Chemodynamic therapy (CDT) shows immense potential in cancer treatment as it not only directly kills tumor cells but also induces anti‐tumor immune responses. However, the efficacy of CDT is hampered by challenges in targeting CDT catalysts specifically to tumors using nanomaterials, along with the limitations of low H2O2 levels and short catalyst duration within the tumor microenvironment. In this study, DNA adjuvant hydrogel to arrange a glucose oxidase‐ferrocene cascade for continuously generating reactive oxygen species (ROS) from glucose in situ for tumor CDT combined with immunotherapy is employed. By precisely tuning the catalyst spacing with DNA double helix, ROS production efficiency is elevated by up to nine times compared to free catalysts, resulting in stronger immunogenetic cell death. Upon intratumoral injection, the DNA hydrogel system elicited potent anti‐tumor immune responses, thereby effectively inhibiting established tumors and rejecting re‐challenged tumors. This work offers a novel platform for integrated CDT and immunotherapy in cancer treatment.