Vascular toxicity of ultra-small TiO2 nanoparticles and single walled carbon nanotubes in vitro and in vivo

Biomaterials. 2015 Sep;63:1-13. doi: 10.1016/j.biomaterials.2015.05.044. Epub 2015 May 31.


Ultra-small nanoparticles (USNPs) at 1-3 nm are a subset of nanoparticles (NPs) that exhibit intermediate physicochemical properties between molecular dispersions and larger NPs. Despite interest in their utilization in applications such as theranostics, limited data about their toxicity exist. Here the effect of TiO2-USNPs on endothelial cells in vitro, and zebrafish embryos in vivo, was studied and compared to larger TiO2-NPs (30 nm) and to single walled carbon nanotubes (SWCNTs). In vitro exposure showed that TiO2-USNPs were neither cytotoxic, nor had oxidative ability, nevertheless were genotoxic. In vivo experiment in early developing zebrafish embryos in water at high concentrations of TiO2-USNPs caused mortality possibly by acidifying the water and caused malformations in the form of pericardial edema when injected. Myo1C involved in glomerular development of zebrafish embryos was upregulated in embryos exposed to TiO2-USNPs. They also exhibited anti-angiogenic effects both in vitro and in vivo plus decreased nitric oxide concentration. The larger TiO2-NPs were genotoxic but not cytotoxic. SWCNTs were cytotoxic in vitro and had the highest oxidative ability. Neither of these NPs had significant effects in vivo. To our knowledge this is the first study evaluating the effects of TiO2-USNPs on vascular toxicity in vitro and in vivo and this strategy could unravel USNPs potential applications.

Keywords: Angiogenesis; Endothelium; Genotoxicity; Ultra-small nanoparticles; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Embryo, Nonmammalian / abnormalities
  • Embryo, Nonmammalian / blood supply
  • Embryo, Nonmammalian / drug effects*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Gene Expression Regulation, Developmental / drug effects
  • Humans
  • Mutagens / chemistry
  • Mutagens / toxicity
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Nanoparticles / ultrastructure
  • Nanotubes, Carbon / chemistry
  • Nanotubes, Carbon / toxicity*
  • Nanotubes, Carbon / ultrastructure
  • Neovascularization, Physiologic / drug effects*
  • Reactive Oxygen Species / metabolism
  • Superoxides / metabolism
  • Titanium / chemistry
  • Titanium / toxicity*
  • Zebrafish / embryology*


  • Mutagens
  • Nanotubes, Carbon
  • Reactive Oxygen Species
  • Superoxides
  • titanium dioxide
  • Titanium