Nanozyme eye drops for retinal barrier penetration and vasculopathy repair.

Retinal neovascularization diseases cause vision impairment due to abnormal blood vessel growth in the retina. Current treatments, including repeated intraocular anti-vascular endothelial growth factor injections, are invasive and often lead to discomfort and complicated hemorrhages. Here, we developed a noninvasive nanozyme eye drop capable of penetrating the fundus to eliminate reactive oxygen species (ROS) and thereby inhibit neovascularization. The nanozyme eye drops consist of liposomes formed by fluorinated and arginine-glycine-aspartic acid-modified phospholipids, which enhance the penetration of ocular barriers. The encapsulated superoxide dismutase-catalase cascade nanozyme within these liposomes allows for efficient ROS scavenging. In vitro and in vivo studies demonstrate that these nanozyme eye drops achieve deep retinal tissue penetration, alleviate oxidative stress, restore mitochondrial function, and suppress aberrant insulin-like growth factor binding protein 6 signaling, thereby inhibiting pathological neovascularization. Enhanced ocular bioavailability and minimal toxicity further underscore its promise as a safe and effective noninvasive treatment for retinal neovascularization diseases.