Visible-Light-Induced Release of Carbon Monoxide: Multifunctionally Treatment for Dry Eye Disease

Dry eye disease (DED) is a multifactorial ocular disorder driven by a reinforcing cycle of oxidative stress, inflammation, and epithelial damage, rendering single-target therapies ineffective. Here, we establish carbon monoxide (CO) gas therapy as a therapeutic modality for DED using a visible-light-activated nanoplatform, TiZr-MOF/CO@F127 (MCF), which simultaneously provides anti-inflammatory, antioxidant, and epithelial-reparative effects. A photosensitive TiZr-MOF loaded with a CO donor [BrMn(CO)₅] enables controlled CO release under visible light, while the thermosensitive F127 hydrogel prolongs corneal retention. In a murine DED model, topical administration of MCF for 5 days achieved 84% corneal epithelial recovery and alleviated corneal inflammation and tissue injury. Mechanistically, CO scavenged reactive oxygen species, suppressed MMP-9 expression, promoted macrophage polarization from M1 to M2 phenotype, reduced inflammatory cytokine production, and enhanced corneal epithelial proliferation. This study establishes a light-activated CO gas therapy strategy for DED and highlights the potential of responsive nanoplatforms for ocular surface disease treatment.