Red Light-Triggered Anti-Angiogenic and Photodynamic Combination Therapy of Age-Related Macular Degeneration

Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently, anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) agents has become the standard treatment for wAMD, while it is still subject to several limitations, including the safety concerns of monthly intravitreal administration and insufficient efficacy for neovascular occlusion. Combined therapy with photodynamic therapy (PDT) and anti-angiogenic agents has emerged as a novel treatment paradigm. Herein, a novel and less-invasive approach is reported to achieve anti-angiogenic and photodynamic combination therapy of wAMD by intravenous administration of a photoactivatable nanosystem (Di-DAS-VER NPs). The nanosystem is self-assembled by reactive oxygen species (ROS)-sensitive dasatinib (DAS) prodrug and photosensitizer verteporfin (VER). After red-light irradiation to the diseased eyes, intraocular release of anti-angiogenic DAS is observed, together with selective neo-vessels occlusion by VER-generated ROS. Notably, Di-DAS-VER NPs demonstrates promising therapeutic efficacy against CNV with minimized systemic toxicity. The study enables an efficient intravenous wAMD therapy by integrating a photoactivation process with combinational therapeutics into one simple nanosystem. A red-light-triggered intraocular drug release strategy is applied to achieve an anti-angiogenic and photodynamic combination treatment of wet age-related macular degeneration (wAMD) via intravenous administration of a photoactivatable nanosystem (Di-DAS-VER NPs). The nanosystem demonstrates strengthened choroidal neovascularization suppression and favorable biosafety profiles in vivo. This novel design has clinical potential for minimally-invasive delivery of combination therapeutics for treating angiogenic eye diseases.image