Regenerative cerium oxide nanozymes alleviate oxidative stress for efficient dry eye disease treatment

Abstract Dry eye disease (DED) is the most common eye disease in ophthalmic consultation except for refractive errors. Therefore, an exploration of valid and alternative therapeutic interventions is essential to feed the urgent medical need. It has been demonstrated that oxidative stress causes multiple adverse effects in the pathogenesis of DED, thence alleviating oxidative stress is an effective therapeutic strategy for the DED treatment. Herein, we developed a cerium oxide nanozyme combined with branched poly(ethylene imine)-graft-poly(ethylene glycol) (bPEI-g-PEG). Owing to its stable hydrophilic chains on the surface reducing the cytotoxicity and loads of amines groups that be combined with cerium ions through coordination bonds, the modified nanozymes (referred to as CNP@bPEI-g-PEG) are water soluble and highly biocompatible. Meanwhile, due to its excellent antioxidant activity, CNP@bPEI-g-PEG nanozymes can mimic the activity of superoxide dismutase and catalase to scavenge intracellular reactive oxygen species (ROS). Experimental studies firmly demonstrated that the modified nanozymes were auto-regenerative and more active in scavenging excessive ROS and alleviating oxidative stress by cerium-element valence state recycling, recovering the morphology of corneal, conjunctival epithelium and the number of goblet cells. The advanced combination may offer a superior therapeutic strategy to deal with oxidative stress for effective treatment of DED.