Light‐Activated Anti‐Vascular Combination Therapy against Choroidal Neovascularization

• Published in: Advanced science Vol. 11; no. 40; pp. e2404218 - n/a
• Main Authors: Xu, Shuting, Li, Jia, Long, Kaiqi, Liang, Xiaoling, Wang, Weiping
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.10.2024; John Wiley and Sons Inc; Wiley
• Subjects: Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; choroidal neovascularization (CNV); Choroidal Neovascularization - drug therapy; Chromatography; combretastatin A‐4; cyanine prodrug; Disease Models, Animal; Drug delivery systems; Humans; Light; Macular degeneration; Mice; Mice, Inbred C57BL; Nanoparticles; near‐infrared (NIR) light‐activation; NMR; Nuclear magnetic resonance; self‐assembled nanoparticles; Side effects; Spectrum analysis; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; self‐assembled nanoparticles; cyanine prodrug; combretastatin A‐4; near‐infrared (NIR) light‐activation; choroidal neovascularization (CNV)
• DOI: 10.1002/advs.202404218
• ISSN: 2198-3844

Choroidal neovascularization (CNV) underlies the crux of many angiogenic eye disorders. Although medications that target vascular endothelial growth factor (VEGF) are approved for treating CNV, their effectiveness in destroying new blood vessels is limited, and invasive intravitreal administration is required. Additionally, other drugs that destroy established neovessels, such as combretastatin A‐4, may have systemic side effects that limit their therapeutic benefits. To overcome these shortcomings, a two‐pronged anti‐vascular approach is presented for CNV treatment using a photoactivatable nanoparticle system that can release a VEGF receptor inhibitor and a vascular disrupting agent when irradiated with 690 nm light. The nanoparticles can be injected intravenously to enable anti‐angiogenic and vascular disrupting combination therapy for CNV through light irradiation to the eyes. This approach can potentiate therapeutic effects while maintaining a favorable biosafety profile for choroidal vascular diseases. Near‐infrared light‐triggered prodrug activation strategy is utilized for anti‐angiogenic and vascular disrupting combination therapy of choroidal neovascularization (CNV). The intravenously administrated photoactivatable nanoparticles can achieve a significant reduction of CNV lesions, without any noticeable side effects in vivo. This approach holds the potential for the accurate delivery of dual‐function anti‐vascular agents to neovascular lesions.