Thermo‐Oxidative Coupling Amplification Effect Unleashed by Tungsten‐Based Polyoxometalate Nanoreactors Enables Synergistic Hyperthermia‐Chemodynamic Therapy

ABSTRACT Monotherapy based on chemodynamic therapy is mostly limited by low reactive oxygen species (ROS) yield and insufficient inhibition efficiency. Inspired by the biomedical potential of polyoxometalates (POMs), we herein report a novel tungsten carbide‐derived POM (WC‐POM) that acts as a bifunctional agent for synergistic hyperthermia and chemodynamic therapy. The WC‐POM exhibits a thermo‐oxidative coupling amplification (TOCA) effect, in which photothermal conversion (49.78% PCE) enhances ROS generation via W 5+ /W 6+ redox cycling, while simultaneously consuming glutathione (GSH) to reshape the tumor microenvironment (TME). This TOCA effect significantly boosts oxidative stress and tumor‐specific cytotoxicity. With a nanosize of ∼14 nm, WC‐POM benefits from enhanced permeability and retention (EPR), enabling efficient tumor accumulation and minimal side effects. This work introduces a new paradigm for POM‐based nanoreactors that integrate photothermal and catalytic functions through the TOCA mechanism for improved cancer therapy.