Tannic Acid–Iron Complex-Based Nanozyme Ameliorates Parkinson’s Disease via Relieving Oxidative Stress and Neuroinflammation

Oxidative stress (OS)-induced neuronal damage and neuroinflammation form a vicious cycle that promotes the progression of Parkinson's disease (PD). Herein, a therapeutic strategy exploiting the tannic acid (TA)–iron (Fe) complex-based nanoparticles (BSA/Fe-TA NPs) that simultaneously relieves brain OS and neuroinflammation is developed for PD therapy. BSA/Fe-TA NPs possess atomically dispersed iron catalytic active sites and display multienzyme-like activities, which can efficiently scavenge reactive oxygen/nitrogen species (RONS). Moreover, they are able to penetrate the blood–brain barrier (BBB) and accumulate in neurons and microglia, thereby mitigating OS in the brain microenvironment via efficient intracellular and extracellular RONS elimination and regulating the polarization of microglia into the anti-inflammatory M2-phenotype to relieve neuroinflammation. After systemic administration, BSA/Fe-TA NPs significantly ameliorate PD progression in a mouse model without inducing adverse effects. Moreover, BSA/Fe-TA NPs can be degraded with the assistance of the clinical iron-chelating ligand deferoxamine, thus accelerating their elimination in vivo.