Page 454 - Environmental Nanotechnology Applications and Impacts of Nanomaterials

Toxicological Impacts of Nanomaterials 431

Studies have shown that in cell culture, QD with a cadmium-selenium
core could be rendered nontoxic with additional coatings. In contrast,
when exposed to air or ultraviolet radiation, they were toxic. This toxi-
+2
city correlated with Cd release in the culture medium, since hepatocytes
are highly cadmium-sensitive. Cadmium release and cytotoxicity could
be attenuated by coating QD with zinc sulfide or bovine serum albumin
prior to exposure to an oxidative environment. These observations illus-
trated that oxidative microenvironments, QD chemical composition, and
cellular sensitivity can all contribute to QD cytotoxicity. This would also
suggest that QD exposure to unintended physical or chemical stressors
during occupational or environmental settings could modulate toxicity.
There are also indications that the size and charge of QD, together with
their intracellular localization, may play a role in their cytotoxicity.
Positively charged CdTe-core, cysteineamine-capped QD were cytotoxic
to PC12 and N9 cells (Lovri´c et al., 2005). In both cases, the 2.3 nm QD
were significantly more cytotoxic than the 5.2 nm QD. This cytotoxicity
could be partially attenuated by N-acetylcysteine but not by α-tocopherol,
suggesting a mechanism other than free-radical generation resulting
+2
from Cd release. The 5.2-nm QD localized to the cytoplasm of N9 cells,
whereas the 2.3 nm localized to the nucleus. Nuclear localization of
cationic QD has been reported previously in mouse fibroblast (3T3) cells
(Bruchez et al., 1998). Whether or not this potentiated cytotoxicity of
2.3-nm QD is directly related to nuclear localization is unknown. It has
been noted that CdSe/ZnS QD can cause nicking of supercoiled plasmid
DNA (Green and Howman, 2005).
In summary, QD offer great potential as therapeutic and diagnostic
agents. Contrary to initial reports, QD can be cytotoxic at concentrations
used in biomedical imaging applications in some cell types. QD size,
charge, shape, and chemical composition, together with cell-specific fac-
tors, can play a role in cytotoxicity. All of these physiochemical proper-
ties play a role in the toxicity of QD and are important determinants for
risk assessment. Table 11.3 lists a number of reports on QD nano-
materials toxicity.

Exposure and Risk Assessment
This chapter has reviewed the literature related to specific nanoparticle
types, which often dictates the kind of studies conducted based on their
intended biomedical applications (e.g., drug delivery, imaging, tissue
engineering). However, more general principles governing the safety of
all particles scenarios need to be evaluated to establish specific nan-
otoxicology safety and testing guidelines after occupational exposure
during manufacture, exposure in academic research laboratories, or envi-
ronmental exposure, either from manufacturing waste or postconsumer