Bioelectric Responsive Nanozymes for Catalytic Control of Lipid Peroxyl Radicals
Lipid peroxyl radicals (ROO·) are terminal propagating species in lipid peroxidation, driving oxidative damage in neurological disorders. Their prolonged lifetime and rapid diffusion within lipid membranes render them difficult to neutralize. Here, we report a bioelectric-responsive TEMPO-doped polydopamine (PDA@TEMPO) nanozyme that sustains catalytic interception of ROO· radicals under persistent oxidative stress. By coupling a PDA redox reservoir with TEMPO catalytic centers, the nanozyme establishes a self-regenerating radical-neutralization cycle via proton-coupled electron transfer (PCET). The π-conjugated framework facilitates charge migration and enables an electric-field-enhanced antioxidant response. In a seizure model, the nanozyme dynamically responds to bioelectric fluctuations, accelerating radical interception and alleviating oxidative stress in neural microenvironments. These findings establish bioelectric-coupled nanozymes as a general strategy for catalytic and sustained regulation of oxidative stress in neural microenvironments, providing a potential therapeutic approach for neurological disorders.