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N. Eter, I. Hahn, F. Levold, E. Endl; Laser-Activated Gold-Nanoparticles as a Potential New Treatment Modality for Exudative Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2982.
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In the last decade nanomaterials have increasingly become subject to investigation for use in antitumor and anitangiogenic therapy. In our study we use laser-activated gold nanorods which are known to be nontoxic and to have excellent absorption properties in the near infrared (NIR) as a potential new treatment modality for choroidal neovascularization in age-related macular-degeneration.
Gold nanorods were coated with both, polyethylenglycol (PEG) to increase biocompatibility and peptides to bind specifically on new growing endothelial cells. Primary retinal endothelial cells and retinal pigment epithelial cells (ARPE-19) were incubated in vitro with gold nanorods. Uptake of nanoparticles was studied by light- and electron microscopy. Cells incubated with and without nanorods were irradiated with a NIR-laser. Afterwards cell death and apoptosis were measured by Hoechst33258 and cPARP-staining, and the influence on proliferation was investigated through EdU-assay. The impact of intracellular or membrane-bound localization of nanorods on irradiation efficiency was analysed by the use of light- and fluorescence microscopy and flow cytometry. Nanorod accumulation in the eye and general biodistribution in vivo was studied histologically in a laser-induced CNV mouse model.
Light microscopy and electron microscopy demonstrated binding and intracellular uptake of coated nanoparticles. Immediately after laser irradiation no effect on cells in terms of cell death could be observed. However, 24h after irradiation a high amount of apoptotic cells could be found and proliferation was reduced. Laser treatment alone without nanoparticles showed no effect on viability and proliferation of neither pigment epithelial cells nor endothelial cells. PEG-coating was observed to be crucial to bypass filter organs and increase circulation time in blood and thereby height accumulation in target tissue. Both, PEG-coated nanoparticles and peptide and PEG-coated plus peptide-coated nanoparticles accumulated exclusively within the areas of choroidal neovascularization and not in healthy tissue.
Specific hyperthermic cell elimination via apoptosis and reduction of cell proliferation can be achieved using biofunctionalized laser-activated gold nanoparticles. Further studies in animals are under way.
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