Rebuilding Ocular Surface Lubrication with a Light-Triggered Hydration-Lubricating Nanoplatform for Dry Eye Disease Therapy.

Dry eye disease (DED) is driven by tear film instability and increased blink-induced interfacial friction, exacerbating epithelial injury and inflammation. The conventional treatments, including artificial tears and hydrogel/contact-lens approaches, all fail to achieve sustained friction control due to limited lubrication durability, rapid clearance, surface dehydration, and foreign-body sensation. Here we developed a light-triggered hydration-lubricating nanoplatform (PAM@HK) that simultaneously restored ocular surface lubrication and enabled on-demand anti-inflammatory therapy. PAM@HK was assembled from an amphiphilic block copolymer that integrated a phosphorylcholine segment to form a robust hydration layer for hydration lubrication and an azobenzene hydrophobic segment for light-switchable honokiol (HK) release. The tribological tests under blink-relevant load and shear revealed that PAM achieved ultralow friction across macroscopic and microscopic scales, evidencing stable hydration lubrication. The near-infrared light irradiation triggered reversible photo-isomerization to greatly accelerate HK release on demand. In DED mouse model, PAM@HK markedly restored corneal integrity and tear film stability, increased tear secretion, preserved conjunctival goblet cells, and suppressed interleukin-6, reactive oxygen species, and pathological keratinization. This work positioned hydration lubrication as a primary therapeutic approach for DED and provided a new low-invasive, light-programmable strategy with superior durability and mechanistic relevance over conventional passive lubrication intervention.