Single-Atom Nanocatalytic Therapy for Suppression of Neuroinflammation by Inducing Autophagy of Abnormal Mitochondria

Catalysts have achieved efficacy in scavenging reactive oxygen species (ROS) to eliminate neuroinflammation, but it ignores the essential fact of blocking the source of ROS regeneration. Here, we report the single-atom catalysts (SACs) Pt/CeO2, which can effectively catalyze the breakdown of existing ROS and induce mitochondrial membrane potential (Δψm) depolarization by interfering with the α-glycerophosphate shuttle pathway and malate-aspartate shuttle pathway, indirectly triggering the self-clearance of dysfunctional mitochondria and thus eradicating the source of ROS generation. In a therapeutic model of Parkinson's disease (PD), Pt/CeO2 wrapped by neutrophil-like (HL-60) cell membranes and modified by rabies virus glycoprotein (RVG29) effectively crosses the blood–brain barrier (BBB), enters dopaminergic neurons entering the neuroinflammatory region breaking down existing ROS and inducing mitophagy by electrostatic adsorption targeting mitochondria to prevent ROS regeneration after catalyst discharge. This strategy of efficiently eliminating ROS at the lesion and fundamentally blocking the source of ROS production can address both symptoms and root causes and provides a mechanism of explanation and action target for the treatment of inflammation-related diseases.