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J. Kim, J. Kim, K.-W. Kim, M. Kim, Y. Yu; Intravenously Administrated Gold Nanoparticles Pass Through Blood-Retinal Barrier Depending on the Particle Size, and Induce No Retinal Toxicity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2418.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate whether intravenously administrated gold nanoparticles (GNPs) could pass through BRB, and are distributed in all retinal layers without cytotoxicity
20 nm and 100 nm GNPs were prepared according to standard procedures. At 1 and 7 days after intravenous injection of GNPs through the tail vein of the C57BL/6J mouse, the eyes were enucleated. Transmission electron microscopy was performed to detect GNPs in the retina. To evaluate the toxicity of GNPs, histological examination and TUNEL assay was performed in the retina, and MTT assays were done in retinal endothelial cells, astrocytes and retinoblastoma cells. Western blotting for ZO-1 and glut-1 in retinal endothelial cells, GFAP in astrocytes, and neurofilament in retinoblastoma cells were performed with the treatment of gold nanoparticles.
After intravenous injection of gold nanoparticles, 100 nm nanoparticle was not detected in the retina whereas 20 nm nanoparticles passed through BRB and were distributed in all retinal layers. 20 nm nanoparticles in the retina were observed in neurons (75 ± 5%), endothelial cells (17 ± 6%), and peri-endothelial glial cells (8 ± 3%), where nanoparticles were bound on the membrane. In the retina, cells containing nanoparticles did not show any structural abnormality and increase of cell death compared to cells without nanoparticles. Gold nanoparticles never affected the viability of retinal endothelial cells, astrocytes, and retinoblastoma cells. Furthermore, gold nanoparticles never lead to any change in expression of representative, biological molecules including zonula occludens-1 and glut-1 in retinal endothelial cells, neurofilament in differentiated retinoblastoma cells and glial fibrillary acidic protein in astrocytes.
Our data suggests that small gold nanoparticles (20 nm) could be an alternative of drug delivery across BRB, which could be safely applied in vivo.
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