Hybrid Biomembrane-Functionalized Nanorobots Penetrate the Vitreous Body of the Eye for the Treatment of Retinal Vein Occlusion

Intravitreal injections of antivascular endothelial growth factor (VEGF) agents are the primary method for treating retinal vein occlusion (RVO). However, the complex structure of eye anatomy presents ocular barriers that impede drug delivery. Additionally, these drugs only manage the complications associated with RVO and fail to address the underlying cause of vessel occlusions. Here, we describe a method that utilizes functionalized magnetically driven nanorobots to overcome ocular barriers and treat RVO. These nanorobots are developed using a hybrid biomembrane that combines stem cell membranes with liposome-derived membranes, enveloping perfluorohexane, iron oxide nanoparticles, and l-arginine. After intravitreal injection, the nanorobots can move directionally through and penetrate the vitreous body to reach the retina, driven by an external magnetic field. Subsequently, the nanorobots actively target the inflammation sites at occluded vessels due to the presence of stem cell membranes. In a rat model of RVO, enhanced targeting and accumulation in ischemic retinal vessels were demonstrated following intravitreal injections. Furthermore, the application of ultrasound triggers the release of l-arginine at the site of occlusion, stimulating the production of nitric oxide, which promotes vasodilation and restores blood flow, thereby achieving excellent therapeutic efficacy for RVO. We believe these methods hold significant promise for overcoming challenges in ocular drug delivery and effectively treating RVO in clinical applications.