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

Abstract 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.