Long-term suppression of retinal degeneration with anti-VEGF agents-loaded hollow mesoporous silica nanoparticles

Age-related macular degeneration (AMD) that leads to degeneration of the overlying photoreceptor in the macula and consequent loss of central vision is the leading cause of irreversible blindness in elderly population. Since vascular endothelial growth factor (VEGF) is pivotal for stimulating neovascularization, monthly intravitreal (IVT) injections of anti-VEGF agents have been used for eliminating neovascularization. However, repeated monthly IVT injections could cause side effects and serious complications. Herein, we report the development of two kinds of anti-VEGF agents (Ranibizumab (Ran) and Aflibercept (Afl))-loaded hollow mesoporous silica nanoparticles for effective treatment of AMD. The designed nanoparticles show no toxicity for both in vitro and in vivo, and could significantly inhibit VEGF-induced proliferation and cell migration. Long-term in vivo experiments in the laser photocoagulation induced choroidal neovascularization (CNV) model for wet AMD show that these nanoparticles effectively inhibit VEGF-induced neovascularization leakage and formation at least 8 weeks upon one IVT injection and therefore are a promising treatment strategy for AMD.