Therapeutic nanocoating of ocular surface

•Formation of a durable and protective therapeutic nanocoating on ocular surface by instilling biomimetic nanoparticles.•Coating with sebocyte membrane that is engineered to overexpress integrin-β1 generates ocular surface adhesive nanoparticles.•Coated nanoparticles that supplement lipid layer and benefit tear film stability can retain up to 24 h in vivo.•Therapeutic values of nanocoating are demonstrated in both mouse and rabbit models of dry eye disease. Topical drug delivery is critical for treating ocular diseases but suffers from low drug availability, long-term frequent administration, and damage to ocular surface. Here, we describe the formation of a durable and protective therapeutic nanocoating on ocular surface by simply instilling biomimetic drug-loaded nanoparticles. This study demonstrates an alternative to protect ocular surface and extend topical delivery of various drugs. [Display omitted] Topical drug delivery is critical for treating ocular diseases but suffers from significant defects including low drug availability, long-term frequent administration, and damage to ocular surface, which largely restrict treatment efficacy and influence quality of life. Here, we describe the formation of a durable and protective therapeutic nanocoating on ocular surface by simply instilling biomimetic drug-loaded nanoparticles. Coating with sebocyte membranes that are engineered to overexpress integrin-β1 generates adhesive nanoparticles that can specifically bind to Arg-Gly-Asp sequence on the fibronectin of ocular epithelium. By virtue of the introduction of sebocyte membranes and the associated lipids, coated nanoparticles can supplement the lipid layer and benefit the stability of tear film. After instillation, formed nanocoating consisting of anchored nanoparticles on ocular surface retains up to 24 h during ex vivo human and in vivo mouse studies. Therapeutic values of this approach are demonstrated in mouse and rabbit models of dry eye disease. Nanocoating carrying clinical dexamethasone effectively improves corneal epithelium recovery, decreases corneal opacity and inflammatory cytokine levels, and restores tear secretion. The present study demonstrates an alternative to protect ocular surface and extend topical delivery of various drugs, supporting the potential of therapeutic nanocoating to treat eye diseases.