title: Intravenously administered gold nanoparticles pass through the blood-retinal barrier depending on the particle size, and induce no retinal toxicity.
abstract: The retina maintains homeostasis through the blood-retinal barrier (BRB). Although it is ideal to deliver the drug to the retina via systemic administration, it is still challenging due to the BRB strictly regulating permeation from blood to the retina. Herein, we demonstrated that intravenously administered gold nanoparticles could pass through the BRB and are distributed in all retinal layers without cytotoxicity. After intravenous injection of gold nanoparticles into C57BL/6 mice, 100 nm nanoparticles were not detected in the retina whereas 20 nm nanoparticles passed through the 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 led to any change in expression of representative biological molecules including zonula occludens-1 and glut-1 in retinal endothelial cells, neurofilaments in differentiated retinoblastoma cells and glial fibrillary acidic protein in astrocytes. Therefore, our data suggests that small gold nanoparticles (20 nm) could be an alternative for drug delivery across the BRB, which could be safely applied in vivo.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine and Seoul Artificial Eye Center, Clinical Research Institute, Seoul National University Hospital, Seoul 151744, Korea. hunin315@paran.com
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Kim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006046:Gold / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D007275:Injections, Intravenous; D008565:Membrane Proteins / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D010750:Phosphoproteins / Q000378:metabolism; D012175:Retinoblastoma / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution / Q000187:drug effects; D062826:Zonula Occludens-1 Protein
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051272:Glucose Transporter Type 1; D008565:Membrane Proteins; D010750:Phosphoproteins; C495677:SLC2A1 protein, human; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D006046:Gold