Selective Treatment of Choroidal Neovascularization by Laser- Activated Gold Nanoparticles: First in vitro Results

Abstract

Purpose: : To establish a new treatment modality for choroidal neovascularization using laser-activated gold nanoparticles.

Methods: : Gold nanorods are synthesized and biofunctionalized for specific targeting of neovascular retinal endothelial cells. Cultured retinal endothelial cells and pigment epithelial cells are incubated with nanorods and treated by laser irradiation to create focused heat shocks due to the laser emission that is absorbed by the nanoparticles. Particle uptake is investigated using light and electron microscopy. Cell death and apoptosis are studied by Hoechst and cPARP staining. Systemic distribution of gold nanoparticles following intravenous application in mice is studied histologically.

Results: : Light microscopy and electron microscopy demonstrate binding and intracellular uptake of coated nanorods. Cell necrosis can be found immediately after laser irradiation, whereas a delayed effect can be induced with even lower laser intensity, as seen in apoptosis measurements after 24h. Cell damage is limited to nanorod targeted cells. Laser treatment modalities alone show no effect on viability of either retinal endothelial cells or pigment epithelial cells. Pharmacokinetic studies in vivo demonstrate that functionalization with PEG is crucial to bypass filter organs in the body and achieve circulation times of the particles, that are necessary for accumulating in the target tissue in the eye.

Keywords: choroid: neovascularization • apoptosis/cell death • laser