Electric‐Field‐Mediated In Situ Electrocatalysis for Enhanced Chemodynamic Therapy and Immunotherapy via 3D Electrode Arrays

Abstract Chemodynamic therapy (CDT) is widely applied in tumor treatment by inducing oxidative damage and immunogenic cell death (ICD). However, its therapeutic effects are constrained by the inherently low endogenous hydrogen peroxide levels and the suboptimal catalytic activity of metal ions. Herein, a tumor synergistic therapy platform based on a 3D electrode array is constructed to enhance local oxidative damage and activate systemic anti‐tumor immunity. By structurally optimizing the electric field distribution and increasing the electrode contact area, alternating current is used to drive electrode polarity switching, enabling dynamic coupling of the valence state conversion of oxygen species (H 2 O → O 2 → H 2 O 2 ) with the valence cycling of cerium ion (Ce 3+ /Ce 4+ ) on the electrode surface. This independent and continuous dynamic cascade electrocatalytic process amplified oxidative stress and disrupted the redox balance in tumor cells, triggering robust ICD. Meanwhile, electrical stimulation reprogrammed tumor‐associated macrophages (TAMs) from M2 to M1. Together, ICD‐induced immunogenicity and reprogrammed TAMs synergistically enhanced the anti‐tumor immune response. In vivo experiments demonstrated that the maturation rate of dendritic cells increased from 12.9% to 65.1%, M1 macrophages increased sevenfold, and tumor‐infiltrating cytotoxic T lymphocytes rose from 12.5% to 38.1%, resulting in the effective inhibition of hepatocellular carcinoma.