Page 453 - Environmental Nanotechnology Applications and Impacts of Nanomaterials

430 Potential Impacts of Nanomaterials

chain methoxy-PEG, or long chain carboxy-PEG QD, but 70 minutes for
long chain methoxy-PEG QD. These studies also demonstrated that QD
remained fluorescent for four months in mice (Ballou et al., 2004), indi-
cating potential long-term exposure.
Other explorations have been conducted on QD of less than 10 nm on
the feasibility of in vivo targeting to specific tissues and cell types that
could escape the reticuloendothelial system filter. These investigators
showed the selective targeting of peptide-coated QD in the vasculature
of lungs and tumors in mice after intravenous injection that demon-
strated it is possible to target QD in living mammals. These QD showed
homing specificity for the relevant vascular sites but did not see accu-
mulation of fluorescence within their targeted tissue (Akerman et al.,
2002). This was in contrast to what was seen earlier with two tumor-
homing peptides F3 and LyP-1 coupled to fluorescein where accumula-
tion not only occurred in the blood or lymphatic vessels, but also in
tumor cells. Nanocrystals can be encapsulated in phospholipid block
polymer-copolymer micelles to increase their biocompatibility in
Xenopus embryos and were found to be stable and nontoxic. QD encap-
sulated in phospholipid micelles were injected in frog oocyte cells for real-
time tracking in embryonic development (Dubertret et al., 2002).
Bioconjugated QD probes with an ABC triblock copolymer linked to a
tumor-targeting ligands and drug functionalities were studied in human
prostate cancer growing in nude mice. This study indicated that these
QD accumulated at tumors both by the enhanced permeability and
retention of tumor sites and by the antibody binding to cancer specific
cell surface biomarkers (Gao et al., 2004).
Derfus et al. (2004) specifically designed a cytotoxicity study with QD
at relevant concentrations for imaging applications and found that MTT
viability decreased in human hepatocytes after treatment with uncoated
UV irradiated or chemically oxidized CdSe QD. A dose-dependent
increase in MTT cytotoxicity was noted in mercaptoundecanoic acid-
coated CdSe QD of three different sizes in African green monkey kidney
cells (Vero cells), HeLa cells, and human hepatocytes (Shiosahara et al.,
2004). Other studies have shown that positively charged cadmium tel-
lerium (CdTe) QD coated with cysteineamine were shown to be cytotoxic
at concentrations used for confocal imaging in N9 murine microglial and
rat pheochromocytoma (PC12) cells (Lovric et al., 2005). Thus, some
QD preparations have demonstrated cytotoxicity in some cell lines at
doses relevant for biomedical applications. Additionally, cells undergoing
rapid migration or those with high membrane turnover are potentially
vulnerable to nonselective uptake of QD by association with the cell
membrane (Parak et al., 2002).
It has been noted that QD size, surface charge, and chemical compo-
sition, along with cell-dependent properties, play a role in cytotoxicity.