title: Intraocular application of gold nanodisks optically tuned for optical coherence tomography: inhibitory effect on retinal neovascularization without unbearable toxicity.
abstract: Bare gold nanospheres have been shown to have anti-angiogenic effects but are optically unfavorable because their resonant wavelength lies in the visible spectrum. Here, we design gold nanodisks with a higher scattering capability than gold nanorods and with a resonant wavelength at near-infrared region - the area where the source of light utilized by optical coherence tomography (OCT) lies. With a physical synthesis system, we then fabricate 160-nm-sized gold nanodisks exhibiting resonant wavelength at 830 nm. The synthesized nanoparticles were successfully visualized in in vivo OCT at concentrations as low as 1 pM. After demonstrating their binding ability to vascular endothelial growth factor (VEGF), we show that they suppress VEGF-induced migration of endothelial cells. Finally, we demonstrate that intravitreally injected gold nanodisks attenuate neovascularization of oxygen-induced retinopathy in mice, in a dose dependent manner, such that they are cleared from the vitreous within 2 weeks without histologic or electrophysiologic toxicity.
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.
authors.forename: Hyun Beom
authors.initials: HB
authors.lastname: Song
authors.affiliation: Center for Nano-Bio Measurement, World Class Laboratory, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.
authors.forename: Jung-Sub
authors.initials: JS
authors.lastname: Wi
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Jo
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Center for Nano-Bio Measurement, World Class Laboratory, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Center for Nano-Bio Measurement, World Class Laboratory, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea. Electronic address: tglee@kriss.re.kr.
authors.forename: Tae Geol
authors.initials: TG
authors.lastname: Lee
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea; Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address: steph25@snu.ac.kr.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006046:Gold / Q000627:therapeutic use*; D056965:Injections, Intraocular; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D012164:Retinal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000295:instrumentation* / Q000379:methods; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors; D006046:Gold
keywords: Angiogenesis inhibitor; Gold nanodisk; Intraocular application; Near-infrared; Optical coherence tomography; Retinal neovascularization