Reaction Mechanisms in Platinum‐Mediated Electrodynamic Therapy

Abstract Electrodynamic therapy (EDT) has emerged as an alternative stimuli‐responsive approach for tumor treatment. The current understanding of its mechanism is that an electric field activates water dissociation on platinum nanoparticles (PtNPs) to produce toxic hydroxyl radicals. Nevertheless, the argument here remains that, if without direct contact with electrodes, the equipotential surfaces of PtNPs may hardly trigger electrocatalytic reactions and thus the induction of any radicals. Clearly, the limited understanding of EDT has considerably hindered its current and further explorations. Herein, the fundamental mechanism of EDT is revealed from the view of heterogeneous catalysis. First and foremost, the free chlorine generated during electrolysis is identified as the crucial reactant, which is not observed previously. Through experimental examinations and density functional theory (DFT) calculations, the fundamental reaction is confirmed to be the catalytic activation of HOCl by PtNPs, resulting in the production of oxygen anion radicals and the corrosion of PtNPs. Moreover, the cytotoxicity and intracellular abnormalities further verify the findings and provide new insight into its in vitro anti‐cancer mechanism. This study not only assists in re‐recognizing the nature of EDT, but also provides core knowledge in guiding its future investigations in catalytic medicine and medical technologies.