The Antiangiogenic Effects of Gold Nanoparticles on Experimental Choroidal Neovascularization in Mice

Abstract

PURPOSE. The purpose of this study was to evaluate the antiangiogenic effect of gold nanoparticles (AuNPs) on experimental choroidal neovascularization (CNV) in mice.METHODS. Choroidal neovascularization was induced by rupturing the Bruch's membrane using laser photocoagulation in C57BL/6 mice. The following day, intravitreal injections of AuNPs were administered. The control group received PBS injection of the same volume. Two weeks after laser injury, CNV lesions were evaluated by examination of choroidal flat-mounts using fluorescein-labeled dextran and immunofluorescence staining with isolectin B4. The effects of AuNPs on endothelial cell tube formation, proliferation, and cytotoxicity were evaluated using human umbilical vein endothelial cells (HUVECs) or human RPE cells. The activity of extracellular signal-regulated kinase (ERK)1/2, protein kinase B (Akt), and focal adhesion kinase (FAK) signaling pathways was also analyzed. RESULTS.The AuNPs reduced the extent of CNV. Mice treated with intravitreal AuNPs injections exhibited a 67.9% reduction in the extent of CNV lesions compared with the control group (P < 0.001). The size of the isolectin B4-labeled area was also significantly smaller in AuNP-treated groups compared with the control group (P < 0.001). Gold nanoparticles decreased vascular endothelial growth factor-induced HUVEC tube formation and proliferation but showed no RPE cell toxicity with the treatment doses administered. The phosphorylation of ERK1/2, Akt, and FAK in HUVECs was suppressed by AuNPs. CONCLUSIONS.Gold nanoparticles can inhibit laser-induced CNV in mice and may have an indication for the treatment of CNV.

Polyvinylpyrrolidone-coated gold nanoparticles inhibit endothelial cell viability, proliferation, and ERK1/2 phosphorylation and reduce the magnitude of endothelial-independent dilator responses in isolated aortic vessels

“…Suppression of ERK1/2 phosphorylation by AuNPs has recently been documented in human umbilical vein ECs. 13 This is also supported by our finding that both modified and unmodified AuNPs inhibited cell proliferation of BAECs. As inhibitors of the ERK1/2 pathway are emerging in clinical trials as anticancer agents, 44 our modified/ unmodified AuNPs may have potential use as anticancer agents.…”

“…Indeed, the antiangiogenic effects of AuNPs have recently been shown. 13 Although unmodified AuNPs were not detectable inside ECs from the TEM images analyzed, we found evidence of their uptake using ICP-MS. A few AuNPs were detected after modification with mPEG and PVP, while an increase in concentration of mPEG-modified AuNPs led to increased vascular uptake. AuNPs were located in the cytoplasm of ECs, but none was located in the nucleus of cells, elastic lamina, or smooth-muscle cell layer.…”

“…12,13 Furthermore, AuNPs can induce oxidative stress and generate reactive oxygen species, which can quench NO, thus affecting vascular function. 14,15 The cytotoxic effects of AuNPs have been shown to be dependent on cell type, NP size, shape, dosage, and in particular, surface chemistry.…”

Gold nanoparticles in ophthalmology

“…Choroidal neovascularization, which can be developed secondary to neovascular AMD, can be induced using laser photocoagulation in mice . Intravitreal injection of 10 pmol of GNP were also shown to decrease the choroidal neovascularization by 67.9% without presenting signs of toxicity against RPE cells.…”

The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells

“…Moreover, AuNPs can significantly inhibit HepG2-conditioned medium (HepG2-CM) activated HUVEC proliferation and migration through the down-regulation of VEGF activity and disruption of cell morphology [13]. AuNPs were shown to inhibit VEGF-induced migration in HUVEC [14] and laser-induced CNV in mice [15]. Fabrication of resveratrol-coated gold nanoparticles can increase the retinal pigment epithelium-derived factor and decrease the VEGF-1 in streptozotocin-induced diabetic rats [16].…”