Abstract

P 287

Laser-activated gold-nanoparticles in the treatment of choroidal neovascularization: First in vitro results

Ina Hahn1, Florian Levold2, Heidrun Keul3, Jürgen Groll3, Gereon Hüttmann4, Elmar Endl2, Nicole Eter1
1Universitäts-Augenklinik Bonn, 2University of Bonn Medical Center, Institute of Molecular Medicine and Experimental Immunology, Bonn, 3RWTH Aachen, DWI, Aachen, 4University of Luebeck, Institute for Biomedical Optics (BMO), Lübeck

Objective
To establish a new treatment modality for choroidal neovascularization (CNV) in age-related macular degeneration using laser-activated gold nanoparticles.
Methods
Gold nanorods were synthesized and biofunctionalized for specific targeting of neovascular endothelial cells. Primary retinal endothelial cells and retinal pigment epithelial cells (ARPE-19) were incubated in vitro with gold nanorods and afterwards treated by laser irradiation of a specific wavelength thereby creating extremely focused heat shocks within a closely defined area. Particle uptake was investigated using light and electron microscopy, cell death and apoptosis were studied by Hoechst and cPARP staining. Systemic pattern distribution of gold nanoparticles following intravenous application in a mouse model was studied histologically.
Results
Light microscopy and electron microscopy demonstrated extracellular binding and intracellular uptake of coated nanoparticles. Cell necrosis could be found immediately after laser irradiation. Furthermore, an additive delayed effect could be induced, as seen in apoptosis measurements 24h after irradiation. In both cases, cell damage was limited to nanorod targeted cells. Laser treatment modalities alone showed no effect on viability of either retinal endothelial cells or pigment epithelial cells. Pharmacokinetic studies in vivo demonstrated that functionalization with PEG was crucial to bypass filter organs and to achieve accumulation of nanoparticles in the target tissue.
Conclusions
Retinal endothelial cells can be targeted by biofunctionalized gold nanoparticles. Cell death of such labelled cells can be achieved by subsequent  laser irradiation which leads to excitation of the incorporated nanorods. Further studies in animals are under way.

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