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Biological Interactions of Functionalized Single-Wall Carbon Nanotubes in Human Epidermal Keratinocytes

Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, North Carolina, USA

Liling Zeng
Andrew R. Barron

Department of Chemistry and the Richard E. Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, Texas, USA

Nancy A. Monteiro-Riviere

Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, North Carolina, USA

Correspondence: Address correspondence to Nancy A. Monteiro-Riviere, PhD, ACT, FATS, Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA. E-mail: NancyMonteiro{at}ncsu.edu

Carbon nanotube–based nanovectors, especially functionalized nanotubes, have shown potential for therapeutic drug delivery. 6-Aminohexanoic acid–derivatized single-wall carbon nanotubes (AHA-SWNTs) are soluble in aqueous stock solutions over a wide range of physiologically relevant conditions; however, their interactions with cells and their biological compatibility has not been explored. Human epidermal keratinocytes (HEKs) were dosed with AHA-SWNTs ranging in concentration from 0.00000005 to 0.05 mg/ml. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability decreased significantly (p < .05) from 0.00005 to 0.05 mg/ml after 24 h. The proinflammatory mediators of inflammation cytokines interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-, IL-10, and IL-1β were also assessed. Cytokine analysis did not show a significant increase in IL-6 and IL-8 in the medium containing 0.000005 mg/ml of AHA-SWNTs from 1 to 48 h. IL-6 increased in cells treated with 0.05 mg/ml of AHA-SWNTs from 1 to 48 h, whereas IL-8 showed a significant increase at 24 and 48 h. No significant difference (p < .05) was noted with TNF-, IL-10, and IL-1β expression at any time point. Transmission electron microscopy of HEKs treated with 0.05 mg/ml AHA-SWNTs for 24 h depicted AHA-SWNTs localized within intracytoplasmic vacuoles in HEKs. Treatment with the surfactant 1% Pluronic F127 caused dispersion of the AHA-SWNT aggregates in the culture medium and less toxicity. These data showed that the lower concentration of 0.000005 mg/ml of AHA-SWNTs maintains cell viability and induces a mild cytotoxicity, but 0.05 mg/ml of AHA-SWNTs demonstrated an irritation response by the increase in IL-8.

Key Words: Cytokines • Keratinocytes • Nanomaterials • Nanotoxicology • Single-Wall Carbon Nanotubes • Skin

International Journal of Toxicology, Vol. 26, No. 2, 103-113 (2007)
DOI: 10.1080/10915810701225133


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