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

Abstract

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 Nanocapsule System Combats Aging by Inhibiting Age-Related Angiogenesis Deficiency and Glucolipid Metabolism Disorders

“…Inadequate VEGF signaling underlies vascular insufficiency in aged mice, , subsequently leading to compromised perfusion, reduced tissue oxygenation, impaired mitochondrial activity, and progressive malfunction of metabolically active organs. Increased circulating VEGF levels maintain youth-like vascular homeostasis and attenuate multiple adverse age-related processes and pathological phenotypes. ,, Our findings strongly support this view and suggest that the biomimetic PCBP nanoheterostructure system is a practical and versatile therapeutic strategy. The system synergizes the therapeutic capacities of nanoparticles, as well as small-molecule drugs.…”

“…Increased circulating VEGF levels maintain youth-like vascular homeostasis and attenuate multiple adverse agerelated processes and pathological phenotypes. 1,49,50 Our findings strongly support this view and suggest that the biomimetic PCBP nanoheterostructure system is a practical and versatile therapeutic strategy. The system synergizes the therapeutic capacities of nanoparticles, as well as smallmolecule drugs.…”

Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases

“…Targeting of the CNV, precise PDT occlusion of neovascular vessels [4] Verteporfin (VER) Photoactivatable nanosystem (Di-DAS-VER NPs) Light triggerd sustained and controlled drug release [230] Table 2 (continued) inducing ferroptosis. Therefore, by sorting the exosomes secreted by ESIONP-induced M1 polarized macrophages, extremely small iron oxide nanoparticles (ESIONPs) incorporated with exosomes (ESIONPs@Exo) can be obtained (Song et al).…”

“…This red light-triggered intraocular drug release NIM delivery system enabled combined anti-angiogenic and PDT treatment of wAMD, showing that this combination treatment greatly alleviated CNV development compared with monotherapies. Moreover, treatment of CNV with Di-DAS-VER NPs showed minimum systemic and ocular toxicities [230]. Although this NIM delivery system for photodynamic therapy targeting retinal neovascular diseases is currently in the early stages of basic research and development, results to date have demonstrated the advantages and immense potential of these photodynamic NIM delivery systems for the treatment of retinal neovascular diseases.…”