Mechanistic Toxicity Evaluation of Uncoated and PEGylated Single-Walled Carbon Nanotubes in Neuronal PC12 Cells

National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, Arkansas 72079, USA.
ACS Nano (Impact Factor: 12.88). 08/2011; 5(9):7020-33. DOI: 10.1021/nn2016259
Source: PubMed


We investigated and compared the concentration-dependent cytotoxicity of single-walled carbon nanotubes (SWCNTs) and SWCNTs functionalized with polyethylene glycol (SWCNT-PEGs) in neuronal PC12 cells at the biochemical, cellular, and gene expressional levels. SWCNTs elicited cytotoxicity in a concentration-dependent manner, and SWCNT-PEGs exhibited less cytotoxic potency than uncoated SWCNTs. Reactive oxygen species (ROS) were generated in both a concentration- and surface coating-dependent manner after exposure to these nanomaterials, indicating different oxidative stress mechanisms. More specifically, gene expression analysis showed that the genes involved in oxidoreductases and antioxidant activity, nucleic acid or lipid metabolism, and mitochondria dysfunction were highly represented. Interestingly, alteration of the genes is also surface coating-dependent with a good correlation with the biochemical data. These findings suggest that surface functionalization of SWCNTs decreases ROS-mediated toxicological response in vitro.

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Available from: Susan Lantz-McPeak, Jun 27, 2014
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    Biomaterials 05/2015; 51. DOI:10.1016/j.biomaterials.2015.01.072 · 8.56 Impact Factor
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    08/2014; 2014:768780. DOI:10.1155/2014/768780
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    • "We also analyzed the GSH content, as GSH is a major intracellular low-molecular-weight thiol compound that plays a critical role in the cellular defense against oxidative stress through scavenging of ROS directly or indirectly in cells (Halliwell and Gutteridge, 2001), and GCL activity , as GCL is the enzyme responsible for catalyzing the synthesis of GSH (Maher, 2006). Our results indicated a significant decrease in the GSH content of the extract exposed to lower concentrations of SWNT- PEG (Fig. 4), a finding that agreed with the results of other studies (Zhang et al., 2011; Valko et al., 2007). The depletion of GSH content induced by SWNT-PEG may be due to an increased production of reactive oxygen species (ROS). "
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