A CeO₂ based ROS-Scavenging and Anti-inflammatory Nanoplatform for Effective Alleviation of Dry Eye Disease

A ROS-scavenging and anti-inflammatory nanoplatform (Hes-CeO₂@PVP/P188) co-loaded with hesperetin and cerium oxide was constructed for dry eye disease (DED) therapy. • The nanoparticles show uniform size (~110 nm), good water solubility, high biocompatibility and negligible hemolysis. • Hes-CeO₂@PVP/P188 exerts synergistic antioxidant effect by mimicking SOD/CAT activities to scavenge ROS and preserve mitochondrial membrane potential. • In DED mice, the nanosystem reduces corneal epithelial damage, promotes tear secretion and alleviates inflammatory infiltration. • The nanoparticles inhibit TNF-α–iNOS–MMP-9 cascade and upregulate HO-1/SOD 2 , breaking the pathological vicious circle of DED. Dry eye disease (DED) is a prevalent chronic ocular disorder characterized by tear film instability and oxidative stress. Herein, a Hes-CeO₂@PVP/P188 nanoparticle system co-loaded with the natural flavonoid hesperetin (Hes) and cerium oxide nanozyme (CeO₂) was developed to achieve synergistic antioxidant and anti-inflammatory effects, thereby effectively alleviating DED. The nanoparticles exhibited a uniform size (~110 nm), good aqueous solubility, and biocompatibility. In vitro assays demonstrated that Hes-CeO₂@PVP/P188 can effectively scavenge reactive oxygen species (ROS), protect cells from H₂O₂-induced oxidative damage, promote wound healing, and preserve mitochondrial membrane potential. In a benzalkonium chloride-induced murine model of DED, the Hes-CeO₂@PVP/P188 nanoparticles significantly reduced corneal epithelial defects, enhanced tear secretion, alleviated inflammatory infiltration, downregulated pro-inflammatory cytokines (including TNF-α, iNOS, and MMP-9), and upregulated the expression of antioxidant markers (including HO-1 and SOD 2 ). The nanoparticles suppressed the TNF-α–iNOS–MMP-9 cascade and effectively broke the pathological vicious cycle of DED. Importantly, the therapeutic efficacy was comparable or superior to that of commercial 0.05% cyclosporine A eye drops in certain indicators. The Hes-CeO₂@PVP/P188 nanoparticles represented a promising dual-functional nanotherapeutic strategy for the treatment of DED. Download: Download high-res image (194KB) Download: Download full-size image Preparation and application of Hes-CeO 2 @PVP/P188 nanoparticles for the alleviation of dry eye disease.