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was associated with a concomitant elevation of malondialdehyde with 20 nm nano-SiO 2 , which
reflects lipid peroxidation. It has been reported by Wang et  al. that oxidative stress plays an
important role in the toxicity of silica nanoparticles on HEK cells, related to particle size (Wang
et al. 2009a).
Furthermore, a strong correlation ( R 2 = 0.956) was demonstrated between the decrease of cell
viability and the increase of ROS production after exposure to 20 nm nano-SiO 2 . In addition, oxy-
gen radicals also resulted in the production of malondialdehyde after the exposure of 20 nm par-
ticles to HEK cells (Wang et al. 2009a). By identifying the mechanisms of internalization, it was
found that silica nanoparticles predominantly penetrate the cells by macropinocytosis and clathrin-
dependent endocytosis, resulting in the intracellular localization by endocytic vesicles as observed
by transmission electron microscopy (Isabelle et al. 2012).
14.3.4.7 Toxicity of QDs
QDs, currently under development for a broad range of biomedical imaging applications, have
also been exposed to induce autophagy in a variety of cell lines, including porcine kidney cells
(Figure 14.4) and human mesenchymal stem cells (Seleverstov et  al. 2006; Stern et  al. 2008).
As the underlying composition (e.g., CdSe, InGaP) and surface chemistries (e.g., protein-coated,
PEGylated, silica coated) of the QDs used in these studies varied significantly, it would suggest
that the unity of the nanoscale size was a significant factor in eliciting this common autophagic
response. Consistent with this hypothesis, autophagy was not induced by QDs that had a tendency
to aggregate to micro-scale particles intracellularly (Seleverstov et al. 2006). The dependence on
the nanoscale size was also noted for neodymium oxide nanoparticle autophagy induction (Chen
et al. 2005), with larger particles having reduced activities.
(a)
500 nm
500 nm
2 μ m
100 nm
(b)
2 μ m
500 nm
500 nm
2 μ m
FIGURE 14.4 Transmission electron micrographs detailing autophagic vacuoles. Porcine kidney cells
(LLC-PK1) were treated for 24 h with either (a) 10 nM CdSe or (b) 100 nM InGaP QDs. The white arrows
represent autophagic vacuoles containing cellular debris. The black arrows represent lysosomal remnants,
which consist of multilamellar vacuoles and electron-dense deposits. (Reproduced from Stern, S.T. et al. 2008.
Toxicol Sci 106:140-152. With permission.)
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