Copper oxide nanoparticles suppress retinal angiogenesis via inducing endothelial cell cuproptosis

Abstract Background: Copper oxide nanoparticles (CuO NPs) have demonstrated versatile applications in antitumor and antibacterial contexts, however, their potential as an anti- angiogenesis agent remains unexplored. This study aims to comprehensively investigate the efficacy of CuO NPs in the treatment of pathological angiogenic retinopathy. Results We demonstrated that CuO NPs possess nano-sized dimensions and exhibit well biocompatibility. In vitro experiments revealed that CuO NPs impede the proliferation, tube formation, migration, and sprouting of HUVECs dose-dependently. Subsequently, in vivo findings showed that CuO NPs effectively suppressed the development of retinal vasculature in a mouse model, as well as alleviate pathological retinal angiogenesis in an oxygen-induced retinopathy (OIR) model. Furthermore, RNA-seq and metabolomic analysis revealed that CuO NPs disrupt the tricarboxylic acid (TCA) cycle and induce cuproptosis. These results were further supported by the evaluation of metabolites and the expression of cuproptosis-related proteins. Conclusions The CuO NPs exhibit potential as effective anti-angiogenic platforms for the treatment of pathological retinal angiogenesis.