Coordination-driven self-assembly of antioxidative and anti-inflammatory cerium-luteolin nanoparticles for effective treatment of ocular alkali burns.

Ocular alkali burns are a severe ophthalmic emergency characterized by excessive production of reactive oxygen species (ROS), persistent inflammation, and corneal neovascularization, often resulting in visual impairment. We develop novel hybrid nanoparticles (CEL NPs) through coordination-driven self-assembly of Ce3+, ε-poly-L-lysine (EPL), and luteolin (Lut) to achieve synergistic ROS scavenging and anti-inflammatory effects. CEL NPs protect human corneal epithelial cells and macrophages from oxidative stress and apoptosis in vitro. CEL NPs also suppress inflammatory responses by inhibiting the NF-κB pathway while activating the Nrf2/HO-1 axis. They exhibit enhanced mucoadhesion and prolonged ocular retention in vivo. In a mouse model of alkali-induced corneal injury, topical CEL NPs markedly accelerate wound closure, reduce neovascularization, attenuate stromal edema, and decrease inflammatory cell infiltration. They outperform the individual components and match the efficacy of dexamethasone, without observable adverse effects. These results demonstrate a safe and effective nanotherapeutic strategy that combines dual redox modulation with anti-inflammatory mechanisms for treating ocular chemical injuries.