Neovascularization-directed bionic eye drops for noninvasive renovation of age-related macular degeneration

The current treatment of wet age-related macular degeneration (wAMD) relies on monthly intravitreal or intravenously injection vascular endothelial growth factor (VEGF) inhibitor photodynamic (PDT) agents to inhibit choroidal neovascularization. However, traumatic local therapy and exogenous long-distance fundus drug delivery often lead secondary eye damage, low efficiency, immunogenic inflammation. Herein, inspired by the natural neovascular targeting ability endogenous low-density lipoproteins (LDL), a noninvasive bionic nano-eye-drop with enhanced ocular penetrability lesion recognizability is developed for enabling PDT wAMD. Verteporfin (VP) as laser-induced agent protected inside hydrophobic core reconstituted LDL (rLDL) vectors. 5-carboxyfluorescein (FAM) conjugated ste-penetratin (PEN, transmembrane peptide) anchored surface rLDL carrier, which enabled nanoparticles (PEN-rLDL-VP) cross blood-retina barrier realizing visual therapy. Following instillation, PEN-rLDL-VP can effectively deliver VP into that overexpress receptors, respond PDT. Only single dose eye-drop PDT, VEGF proinflammatory intercellular adhesion molecule-1 (ICAM-1) proteins are significantly down-regulated in vivo, implicates inhibition inflammation alleviation. This study presents an attractive non-invasive strategy