Negatively charged gold nanoclusters protect against diabetic cardiomyopathy by inhibiting mitophagy

Abstract

Diabetic cardiomyopathy is a disorder of the heart muscle in people with diabetes and has seriously threatened people's life. Herein, we developed gold nanoclusters (AuNCs) stabilized by two modification ligands, 3-mercaptopropionic acid (MPA) and N-acetyl-L-cysteine (NAC), and three different charged ligands, positive charged polyetherimide (PEI), relatively positive charged polyethylene glycol (PEG), and negatively charged polyvinyl pyrrolidone (PVP) for the therapy of diabetic cardiomyopathy. PVP-MPA stabilized AuNCs (PVP-M) were found to most effectively protect cardiac mitochondria against perturbations, stabilize the mitochondrial membrane potential, and inhibit overexpressed mitochondrial ROS via different pathways. In addition, PVP-M have a protective effect in cardiomyopathy cell models, by up-regulating cell activity under high-fat environmental conditions and enhancing the degradation of excessively produced lipid peroxides, thereby reducing the loss of cell viability. Our findings indicate PVP-M are promising in the treatment of cardiovascular disease in diabetic patients.