title: Anti-angiogenic effect of bare titanium dioxide nanoparticles on pathologic neovascularization without unbearable toxicity.
abstract: Local application requires fewer nanoparticles than systemic delivery to achieve effective concentration. In this study, we investigated the potential toxicity and efficacy of bare titanium dioxide (TiO2) nanoparticles by local administration into the eye. Mono-disperse, 20nm-size TiO2 nanoparticles did not affect the viability of retinal constituent cells within certain range of concentrations (~1.30μg/mL). Furthermore, local delivery of TiO2 nanoparticles did not induce any significant toxicity at the level of gene expression and histologic integrity in the retina of C57BL/6 mice. Interestingly, at the low concentration (130ng/mL) without definite toxicity, these nanoparticles suppressed in vitro angiogenesis processes and in vivo retinal neovascularization in oxygen-induced retinopathy mice when they are administered intravitreally. Taken together, our results demonstrate that even TiO2 nanoparticles can be safely utilized for the treatment of retinal diseases at the adequate concentration levels, especially through local administration.
  
  
  BACKGROUND
  In this paper the local application of titanium dioxide is described as a local treatment for retinal diseases associated with neovascularization. While these nanoparticles have known systemic toxicity, this work demonstrates that when applied locally in a mouse model, they can be used without observable toxicity even in their native forms.
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Jo
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical 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 Convergence, World Class Laboratory, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea; Department of Chemistry and KI for the NanoCentury, KAIST, Daejeon, Republic of Korea.
authors.forename: Jin Gyeong
authors.initials: JG
authors.lastname: Son
authors.affiliation: Center for Nano-Bio Convergence, World Class Laboratory, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.
authors.forename: Nam Woong
authors.initials: NW
authors.lastname: Song
authors.affiliation: Division of Industrial Metrology, Center for New Functional Materials Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.affiliation: Center for Nano-Bio Convergence, 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, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, 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: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D014025:Titanium / Q000737:chemistry*
chemical_list: C009495:titanium dioxide; D014025:Titanium
keywords: Titanium dioxide; angiogenesis inhibitor; nanoparticles; pathologic angiogenesis; toxicity