Biodistribution and toxicological study of PEGylated single-wall carbon nanotubes in the zebrafish (Danio rerio) nervous system

Toxicol Appl Pharmacol. 2014 Nov 1;280(3):484-92. doi: 10.1016/j.taap.2014.08.018. Epub 2014 Aug 26.

Abstract

Nanotechnology has been proven to be increasingly compatible with pharmacological and biomedical applications. Therefore, we evaluated the biological interactions of single-wall carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG). For this purpose, we analyzed biochemical, histological, behavioral and biodistribution parameters to understand how this material behaves in vitro and in vivo using the fish Danio rerio (zebrafish) as a biological model. The in vitro results for fish brain homogenates indicated that SWNT-PEG had an effect on lipid peroxidation and GSH (reduced glutathione) content. However, after intraperitoneal exposure, SWNT-PEG proved to be less biocompatible and formed aggregates, suggesting that the PEG used for the nanoparticle functionalization was of an inappropriate size for maintaining product stability in a biological environment. This problem with functionalization may have contributed to the low or practically absent biodistribution of SWNT-PEG in zebrafish tissues, as verified by Raman spectroscopy. There was an accumulation of material in the abdominal cavity that led to inflammation and behavioral disturbances, as evaluated by a histological analysis and an open field test, respectively. These results provide evidence of a lack of biocompatibility of SWNTs modified with short chain PEGs, which leads to the accumulation of the material, tissue damage and behavioral alterations in the tested subjects.

Keywords: Behavioral; Biocompatibility; Biodistribution; Oxidative stress; SWNT-PEG; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain / metabolism*
  • Glutathione / analysis
  • Histocytochemistry
  • Male
  • Microscopy, Electron, Transmission
  • Nanotubes, Carbon / toxicity*
  • Nanotubes, Carbon / ultrastructure
  • Polyethylene Glycols / pharmacology*
  • Spectrum Analysis, Raman
  • Thiobarbituric Acid Reactive Substances / analysis
  • Tissue Distribution / physiology
  • Zebrafish / metabolism*

Substances

  • Nanotubes, Carbon
  • Thiobarbituric Acid Reactive Substances
  • Polyethylene Glycols
  • Glutathione