Single-atom Pt-N-C nanozyme targets Rara/Wnt/β-catenin axis for diabetic cardiomyopathy treatment.

BACKGROUND AND PURPOSE: Diabetic cardiomyopathy (DCM) lacks effective therapies because of complex mechanisms. This study aims to develop a single-atom nanozyme for integrated antioxidant and signalling regulation in DCM. EXPERIMENTAL APPROACH: A graphene quantum dot-templated single-atom Pt-N-C nanozyme (PtsaN-C) was synthesised for all-trans retinoic acid (ATRA) delivery (PtsaN-C@ATRA). In vitro antioxidant activity and in vivo efficacy were evaluated in DCM mice, combined with scRNA-seq for mechanistic analysis. KEY RESULTS: PtsaN-C@ATRA improved cardiac function, reduced fibrosis/apoptosis and activated the Rara/Wnt/β-catenin axis to promote cardiomyocyte differentiation. CONCLUSIONS AND IMPLICATIONS: PtsaN-C@ATRA represents a novel strategy merging nanozyme catalysis with transcriptional regulation, offering potential for clinical translation in DCM.