Regenerative cerium oxide nanozyme for cataract treatment via oxidative stress regulation

Abstract

As the world's leading blinding eye disease, cataract pathogenesis is closely related to reactive oxygen species (ROS)-mediated oxidative damage to the lens. Surgical intervention has limitations, necessitating non-invasive antioxidant treatment strategies. This study used branched-chain polyethylenimine grafted polyethylene glycol (bPEI-g-PEG) to obtain cerium oxide nanozyme nanoparticles (CNP) with excellent stability, evaluating their physicochemical properties, antioxidant activity and biological effects. The therapeutic potential of CNP was analyzed using oxidative damage model in human lens epithelial cells (HLECs) and rat cataract models. CNP mimic the activities of superoxide dismutase (SOD) and catalase (CAT) through a dynamic Ce³⁺/Ce⁴⁺ redox cycle on their surface. In simulated in vitro oxidative stress environments, CNP demonstrate a repeatable (ROS) scavenging capability, thus exhibiting the distinctive "oxidative regeneration" characteristic. CNP significantly attenuated HLEC oxidative damage by inhibiting epithelial-mesenchymal transition (EMT), maintaining mitochondrial homeostasis, and enhancing lens proteolysis. In UV-induced rat cataracts, CNP treatment reduced lens turbidity and improved lens fiber structural integrity. TUNEL/DHE double staining confirmed CNP effectively scavenged lens ROS and inhibited apoptosis. bPEI-g-PEG modification solved CNP stability defects, supporting ophthalmic dosage form development. CNP demonstrates potential for non-surgical cataract prevention and treatment through synergistic mechanisms, providing a new therapeutic strategy for oxidative stress-related eye diseases.