Toxicological Effects of Metal Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 194

corona may also facilitate the receptor-mediated endocytosis and the subsequent
intracellular transport of gold nanorods to endosomes and lysosomes (Alkilany et al.
2009; Wang et al. 2013a).
Only a few studies have been published assessing the toxic potential of gold
nanoshells. Most of these studies reported a noncytotoxic behavior of these nano-
materials in different cell lines, such as human hepatocellular carcinoma cells (Liu
et al. 2010) or human prostate cancer cells (Stern et al. 2007). Likewise, PEG-coated
silica-gold nanoshells did not display cytotoxic effects in human breast adenocarci-
noma cells (SK-BR-3) (Hirsch et al. 2003) nor did immunoglobulin-coated nanoshells
(Loo et al. 2005).
Taken together, the cytotoxicity studies of gold nanomaterials clearly demonstrate
that in contrast to the inertness of gold in bulk form, nanosized gold particles can
induce cytotoxic effects dependent on their size and surface coatings. This empha-
sizes the need to investigate the toxic potential of engineered gold nanoparticles on
a case-by-case basis.
In an interdisciplinary research effort, Midander et al. investigated cytotoxic-
ity of micro- and nanosized copper particles in relation to the particle properties
(Midander et al. 2009). The nanosized copper particles (100 nm, 80 µg/mL, 18 h)
were found to induce a significantly higher percentage of cell death in lung epi-
thelial cells (A549) in comparison to their microsized counterparts. Moreover, the
nanoparticles released greater amounts of copper per quantity of particles compared
to the microsized copper particles. The effects, however, could be correlated only to
a small extent to the fraction of released copper, indicating that the cytotoxic effects
were caused mainly by the particles themselves (Midander et al. 2009). A correlation
between size and toxicity for copper nanoparticles was also found by Prabhu et al.
using 40, 60, and 80 nm copper particles at concentrations of 10-100 µM to expose
dorsal root ganglion (DRG) cells. Although all copper nanoparticles displayed cyto-
toxicity, the effects of 40 nm sized copper particles on cell death (LDH assay) and
cellular metabolic activity (MTS-assay) were much more pronounced (Prabhu et al.
2010).
Regarding toxicological studies of platinum nanoparticles, current literature
data are limited. Nanoscaled platinum particles of different shapes in the size
range of 11-35 nm and their effects on A549 cells and human umbilical vein endo-
thelial cells (HUVEC) have been investigated by Elder et al. (2007). Colloidal
platinum nanoflowers, multipods, and spheres were taken up by the cells but did
not induce significant cytotoxic effects, such as oxidative stress (DCF assay), cell
death (LDH assay), or inflammatory markers (Il-6-ELISA) at concentrations up
to 250 µg/ml. Similar results were found for 5-10 nm platinum nanoparticles of
100% purity when these were exposed to A549 or HaCaT cells in a more recent
study (Horie et al. 2011). Cell viability (MTT assay), cell proliferation (clonogenic
assay), apoptosis induction (caspase-3 activity), intracellular ROS level (DCFH
assay), and lipid peroxidation level (DPPP assay) were not influenced by these pris-
tine platinum nanoparticles although the nanoparticles were internalized by the
cells (Horie et al. 2011). Likewise, nanoscaled platinum particles of different sizes
(12 and 66 nm) did not induce oxidative stress in human colon carcinoma cells
(HT29; Pelka et al. 2009). Albeit caution is advised to draw general conclusions