title: Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes.
abstract: 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)-alpha, IL-10, and IL-1beta 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-alpha, IL-10, and IL-1beta 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.
authors: Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, North Carolina 27606, USA.
authors: Leshuai W
authors: LW
authors: Zhang
authors: Liling
authors: L
authors: Zeng
authors: Andrew R
authors: AR
authors: Barron
authors: Nancy A
authors: NA
authors: Monteiro-Riviere
mesh_terms: D015119:Aminocaproic Acid / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D004338:Drug Combinations; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D020442:Poloxamer / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D004338:Drug Combinations; D037742:Nanotubes, Carbon; D013501:Surface-Active Agents; D020442:Poloxamer; D015119:Aminocaproic Acid