Biomedical Engineering Reference
In-Depth Information
FIGURE 20.5
Mechanism of SWCNT uptake by cell via endocytosis pathway.
from mitochondrial disruption and the release of proapoptotic factors. Several mechanisms may be
based on the toxicity of CNTs as described below [1].
20.7.1 f
ree
r
adIcal
f
orMatIoN
The main cause of the toxicity is related to the oxidative stress by free radical formation. These
free radicals oxidize lipids, proteins, and DNA. Oxidative stress can upregulate transcription fac-
tors sensitive to redox activator protein-1, and kinases that cause inflammatory responses. Slow
clearance caused by agglomeration or accumulation of these NPs can produce free radicals in the
organs of the reticuloendothelial system (RES) such as the spleen, lungs, and kidneys, which are
easy targets for oxidative stress [9].
20.7.2 r
eactIve
o
xygeN
s
pecIes
Reactive oxygen species (ROS) are chemically reactive oxygen-containing molecules which are
formed as by-products of normal oxygen metabolism. However, the level of ROS may increase due
to environmental stress, such as exposure to radiation, foreign particles, and so on. ROS can lead to
detrimental effects on the cells, such as apoptosis, DNA damage, oxidation of amino acids, and inac-
tivity of enzymes. Studies have shown that damaged DNA SWCNTs cause changes in the cell cycle
and apoptosis signal by the generation of ROS. Most of the cells cultured in media containing CNTs
alter the G1 phase of their cell cycle. Wang et al. have found that apoptosis was induced in PC12 cells
by 4-5 times higher concentrations of ROS in cells exposed to SWCNTs (200 g/mL) [15].
20.7.3 I
Ncreased
I
NflaMMatory
r
espoNses
Inflammatory responses produced by exposing mice to carbon black was compared to asbestos
and MWCNTs. While carbon black initiated a normal foreign body response, where the immune
system recognized and destroyed foreign particles, MWCNTs and asbestos exposure increased the
release of polymorphonuclear leukocytes and protein exudation, indicating an increased inflamma-
tory response. The same group also showed the difference in toxicity levels between short and long
MWCNTs. They attributed the increased inflammatory response of long MWCNTs and asbestos to
“frustrated phagocytosis” in which the macrophages are unable to engulf the long needle-shaped
CNTs. By contrast, in another study done on a mouse macrophage RAW 264.7 cell line, CNTs
induced ROS-related necrosis, apoptosis, and chromosomal damage, but did not induce an inflam-
matory response [16].
