Human Toxicology and Effects of Nanoparticles - Environmental and Human Health Impacts of Nanotechnology - page 373

emission spectra of which varies according to particle size. This makes quantum
dots a potentially useful alternative to the relatively unstable fl uorescent organic
dies currently used for immunofl uorescence (Xing et al. , 2007). Perhaps more inter-
estingly, quantum dots have also been developed for use in medical applications
since they are relatively photostable and their light emission can be detected from
a whole organism using digital imaging devices (Giepmans et al. , 2005 ; Jaiswal
et al. , 2003). Targeting of the quantum dot to specifi c locations in the body, for
example a tumour, may be possible through the manipulation of particle size and
surface modifi cations (e.g. antibodies), therefore allowing diagnosis of disease
without the need for surgery (Ballou et al. , 2004 ; Michalet et al. , 2005 ). The advan-
tages of using quantum dots as diagnostic tools have been demonstrated in a
number of studies (Ballou et al. , 2004 ; Xing et al. , 2007). For example, one study by
Gao and Nie (2004) reported that both subcutaneous and systemic injection resulted
in the accumulation of multifunctional quantum dots probes within human prostate
tumours grown in mice. Accumulation was mediated due to the enhanced perme-
ability of blood vessel walls in the tumour site, as well as the antibody binding to
cancer - specifi c cell surface biomarkers.
Quantum dots are often coated with a shell consisting of zinc sulfi de. This shell
has been introduced to improve the stability of the cadmium containing core, with
the aim to reduce leaching of this toxic component (Derfus et al. , 2004 ). In addition,
further surface modifi cations include organic (neutral charge and hydrophobic),
amino or amine (positively charged and hydrophilic) or carboxyl (negatively
charged and hydrophilic) chemically bonded groups. The polymer (PEG) can also
be attached to the particle surface, with the aim that PEG provides a steric repul-
sive barrier resulting in lack of recognition by blood proteins and phagocytic cells
(Porter et al. , 1992 ; Gref et al. , 1994). The consequence of avoiding uptake by
macrophages is that the particles increase their residence time in the blood and
increase their chance of reaching the required target.
Although quantum dots appear to be an effective bio-imaging diagnostic tool,
knowledge relating to their toxicity is fairly limited. Unlike the low toxicity, low
solubility carbon black and TiO 2 nanoparticles, these nanoparticles include con-
stituents which are inherently toxic. For example, cadmium is associated with renal
toxicity. A limited number of studies have investigated quantum dot toxicity. Derfus
et al. (2004) identifi ed that uncoated cadmium selenide quantum dots induced a
concentration dependent toxicity in hepatocytes, which was related to a release of
free cadmium ions (Cd 2+ ) from the quantum dot core. Derfus et al. (2004) hypoth-
esised that the addition of a shell of zinc sulfi de, dihydrolipoic acid or a polymer
based material to quantum dots would reduce their toxicity. However, other studies
have shown cadmium ions to be released from quantum dots both with and without
a shell layer (Kloepfer et al. , 2003). It has been suggested that the shell might in
fact decrease the stability of the quantum dots and subsequently cause a greater
toxic response (Michalet, et al. 2005 ).
The impact of coating on quantum dot stability and toxicity varies substantially
between different studies from different groups. The cause of this variation is
unclear, but is likely to stem from differences in the properties of the quantum dots
used, as well as their quality. Quantum dots with a negatively charged, carboxylated