A CeO₂ based ROS-scavenging and anti-inflammatory nanoplatform for effective alleviation of dry eye disease.

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 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 SOD2). 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.