Ultrasmall platinum nanozymes as broad-spectrum antioxidants for theranostic application in acute kidney injury

Acute kidney injury (AKI) is a common kidney disease with high mortality rate, while surprisingly, the supportive treatment and renal replacement are the only available clinical treatment options to date. The onset of AKI is often triggered by excessive toxic reactive oxygen/nitrogen species (RONS), and hence, the development of antioxidants with high renal accumulation and effective renal clearance is highly demanded to consume RONS in the kidneys. In this study, we developed ultrasmall polyvinylpyrrolidone-coated platinum nanoparticles (Pt NPs-PVP, ~3 nm) as multienzyme mimetics (catalase, peroxidase, and superoxide dismutase). Thanks to their excellent RONS scavenging ability, Pt NPs-PVP effectively reduced the hydrogen peroxide induced cellular damage. Analytical (inductively coupled plasma mass spectrometry) as well as imaging (photoacoustic and computed tomography) techniques revealed the preferential renal uptake and high enrichment of ultrasmall Pt NPs-PVP after intravenous administration, offering remarkable relief of the clinical symptoms of glycerol-induced AKI mice without any apparent systemic toxicity in vivo. Importantly, because of their ultrasmall size, Pt NPs-PVP exhibited rapid excretion from healthy mice, presenting relatively low toxicity and side effects. In conclusion, our work demonstrated ultrasmall Pt nanozyme as a state of the art antioxidant for dual-modal imaging guided treatment of AKI with improved treatment efficacy.