Ultrasmall Copper-Based Nanozyme Eye Drops for Effective Antioxidative Therapy of Ocular Surface Diseases

Developing an effective strategy to mitigate the excessive production of reactive oxygen species (ROS) caused by diverse factors is crucial for preventing ocular surface diseases. However, due to the inherent characteristics of ocular barriers, the therapeutic efficacy of conventional eye drops remains unsatisfactory. Copper-based nanozymes are known for their enzyme-mimetic ROS scavenging abilities. In this study, we report a simple, ecofriendly, one-step synthesis of ultrasmall copper Cu_5.4O nanoparticles (NPs) as antioxidant and anti-inflammatory nanozymes in eye drop formulations. The Cu_5.4O NPs showed strong hydrogen peroxide (H₂O₂) scavenging ability and reduced intracellular ROS in corneal cells <i>in vitro</i>. <i>In vitro</i> hemolysis studies and <i>in vivo</i> assessments of ocular biocompatibility confirmed that Cu_5.4O NP eye drops are safe for application as nanomedicines in ophthalmic formulations. Moreover, in the H₂O₂-induced corneal oxidative damage model in mice, Cu_5.4O NP eye drops effectively scavenged ROS and reduced inflammation, thereby providing protection against oxidative damage and facilitating epithelial regeneration. Collectively, the capabilities of Cu_5.4O NP-based eye drops offer valuable insights into developing new treatment strategies for ROS-mediated corneal diseases and support the use of nanomaterials in clinical applications.