Phenol-like group functionalized graphene quantum dots structurally mimicking natural antioxidants for highly efficient acute kidney injury treatment

Acute kidney injury (AKI) is a syndrome characterized by rapid loss of renal excretory function with high in-hospital mortality. The excess generation of reactive oxygen species (ROS) in the kidneys during AKI has been considered a major cause of renal failure. Currently available antioxidants for AKI treatment often lack the required antioxidative efficacy or renal accumulation rate. Herein, inspired by the structure of natural phenolic antioxidants, phenol-like group functionalized graphene quantum dots (h-GQDs) with both high ROS scavenging efficacy and renal specificity are constructed for AKI antioxidative therapy. Similar to natural polyphenols, the abundant phenol-like groups on h-GQDs are demonstrated to be the active components exerting antioxidative effects. Further exhaustive mechanistic investigations indicate that the ultrahigh antioxidative activity of h-GQDs originates not solely from the phenol-like groups, but also from the synergy between adjacent phenol-like groups, as well as the removal of unfavorable carbonyl groups on h-GQDs. In AKI mice, h-GQDs can effectively protect the kidneys from oxidative injury with only a one-sixteenth dose of the clinical antioxidant N-acetylcysteine (NAC) and show no evidence of toxicity. The findings of this study will facilitate development of high-performance carbon-based antioxidative platforms via structure–activity relationships for treating AKI and other ROS-related diseases.