Copper oxide nanoparticles suppress retinal angiogenesis via inducing endothelial cell cuproptosis

Background: Copper oxide nanoparticles (CuO NPs) exhibit antitumor activity; however, their potential as an antiangiogenesis agent is unknown. Materials & methods: The antiangiogenesis properties of CuO NPs were evaluated in vitro and in vivo and the underlying mechanism was examined using RNA sequencing and metabolomic analyses. Results: CuO NPs inhibited endothelial cell function in vitro. They also mitigated retinal vasculature development and alleviated pathological retinal angiogenesis in vivo. RNA sequencing and metabolomic analyses revealed that CuO NPs disrupt the tricarboxylic acid cycle and induce cuproptosis, which was further supported by evaluating cuproptosis-related metabolites and proteins. Conclusion: CuO NPs may be an effective antiangiogenic agent for the treatment of retinal angiogenesis.