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H. Salehi-had, T. Hisatomi, J. W. Miller, S. Guccione; Targeting Choroidal Neovascular Membranes With Nanoparticles Binding Alpha V Beta 3. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2962.
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The integrin vβ3 is differentially expressed on neovascular endothelial cell in ocular and tumor angiogenesis. The purpose of this study is to evaluate whether a novel intravenously injectable vβ3 cross-linked liposome nano-particle (NanoVast) can target the abnormal blood vessels in the laser injury model of choroidal neovascularization (CNV) in rats.
Four laser burns were created in one eye of each Brown Norway rat. Fluorescein angiography (FA) with intraperitoneal injection of 2% fluorescein sodium was used to confirm the development of CNV lesions. Rhodamine-labeling of NanoVast (Rd-NanoVast) was used to evaluate delivery of the particles to CNV. NanoVast carrying a green fluorescing protein (GFP) plasmid (NanoVast-GFPg) was used to evaluate the ability of the particles to deliver a gene to the neovascular endothelial cells. Rd-NanoVast-GFPg particles were injected intravenously 1, 2, or 3 weeks after laser injury. The expression of GFP was evaluated with in vivo imaging using the Topcon camera with fluorescein filter settings, days 1, 2, and 3 after injection of particles. Choroidal flat mounts were performed at the same time points to confirm the localization of Rd-NanoVast to CNV and the expression of GFP. Negative controls were evaluated under the same conditions without injection of NanoVast or following injection of non-targeted rhodamine labeled liposome particles carrying GFP-plasmid.
FA documented leaky CNV lesions one week after laser injury with a slight increase in size and leakage by weeks 2 and 3. GFP plasmid expression was seen in vivo on days 1, 2, and 3 after injection of Rd-NanoVast-GFPg. The delivery of rhodamine dye and the expression of GFP plasmid in CNV was confirmed by performing confocal microscopy on choroidal flat mounts. The negative controls showed no fluorescence above the background level in vivo or in the flat mounts. There was no evidence of increased fluorescence in the normal retinal or choroidal vasculature.
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