Page 419 - Environmental Nanotechnology Applications and Impacts of Nanomaterials

402 Potential Impacts of Nanomaterials

Immortalized nontumorigenic human epidermal (HaCaT) cells exposed
to SWCNT suggest that carbon nanotubes may be toxic to epidermal ker-
atinocyte cultures (Shvedova et al., 2003). Significant cellular toxicity
was found when unrefined SWCNT were exposed to cells for 18 hours. The
inflammatory markers of irritation/inflammation were not conducted in
this cell line. Previously, our lab has demonstrated significant differences
in the toxicological response between immortalized versus primary ker-
atinocytes (Allen et al., 2001). Gene expression profiling was conducted
on human epidermal keratinocytes exposed to 1.0 mg/ml of SWCNT that
showed a similar profile to alpha-quartz or silica. Alpha-quartz is con-
sidered to be the main cause of silicosis in humans. Genes not previously
associated with these particulates from the structural protein and
cytokine families were significantly expressed (Cunningham et al., 2005).
In addition to toxicity studies, data have been collected when SWCNT
have been evaluated as therapeutic agents for drug and vaccine deliv-
ery (Smart et al., 2006). Drug delivery can be enhanced by many types
of chemical vehicles, including lipids, peptides, and polyethylene glycol
(PEG) derivatives. Strategies using SWCNT and SWCNT-streptavidin
conjugates as biocompatible transporters have shown localization within
human promyelocytic leukemia (HL60) cells, and human T (Jurkat)
cells via endocytosis. Functionalized SWCNT exhibited little toxicity to
the HL60 cells, but the SWCNT–biotin-streptavidin complex caused
extensive cell death (Kam et al., 2004). Other studies have demon-
strated that functionalized, water-soluble SWCNT derivatives modi-
fied with a fluorescent probe can translocate across the cell membrane
of fibroblasts without causing toxicity (Pantarotto et al., 2004). The
translocation pathway remains to be elucidated. It has been shown that
the solubility of functionalized SWCNT is controlled by the length of the
hydrocarbon side chain (Zeng et al., 2005). Other studies comparing
SWCNT as purchased, purified SWCNT or functionalized with glu-
cosamine showed significant effects on in vitro fibroblast cell function
and demonstrated that chemical modifications can alter their cellular
interactions (Nimmagadda et al., 2006). Three different water-
dispersible SWCNT were exposed to fibroblasts to determine if the
degree of functionalizations affects its response in cells. These investi-
gators found that as the side-wall functionalization increases, SWCNT
suspensions appear to be less cytotoxic and that functionalized tubes
were less cytotoxic than the surfactant stabilized tubes (Sayes et al.,
2006). This is consistent with the fullerene data reviewed above, but with
some of the same complications in interpreting these results originat-
ing from aggregation effects.
Purified SWCNT did not stimulate the release of nitric oxide by
murine macrophages in culture, their uptake was low and cell surface
morphology was unchanged (Fiorito et al., 2006). The cytotoxicity of