Biomedical Engineering Reference
In-Depth Information
In some cases, such as diamond nanoparticles [59], there is no significant detectable ROS
production, hence additional research is necessary to finalize all aspects of nonimmunotox-
icity. For example, granulocyte/macrophage colony stimulating factors (GM-CSF), inter-
leukin 4 (IL-4), and interferon gamma appear to be important cytokines for stimulation of
macrophages and oxidative activity [60]. The concentration of ROS can be determined by
using indicators such as 2′,7′-difluorescein diacetate (DFDA) for cerium oxide nanoparticles
[61] and dichlorodihydrofluorescein diacetate (DCHFDA) for iron oxide nanoparticles
[62], which fluoresce when oxidized by ROS [63]. Respiratory immunotoxicity has been
observed in rats administered zinc oxide nanoparticles by intratracheal instillation [64].
A size-dependent activation of the inflammatory response was reported for 15-nm-sized
silver particles by the detection of TNF-α, MIP-2, and IL-1β [65]. The expression of
inflammatory related genes such as IL-1, IL-6, TNF-α, iNOS, and COX-2 increased in
cultured peritoneal macrophages that were induced by silica nanoparticles [66].
Carcinogenicity and Reproductive Toxicity
Long-term studies are required in order to determine carcinogenic potential of nanomateri-
als, particularly those without known significant toxicities. Toxicity of single-walled carbon
nanotubes (SWCNTs) and multiwalled carbon nanotubes (MWCNTs) have been studied
extensively. However, due to the diverse physical properties of carbon-based materials and
the possibility for proper functionalization with chemical groups, different biological out-
comes have been reported. Injection of SWCNTs into the bloodstreams of mice revealed no
evidence of toxicity over 4 months [67]. In another study, MWCNTs were present in the
subpleural wall and subpleural macrophages after 6 h of inhalation [68]. DNA damage has
been shown in embryonic stem cells exposed to MWCNTs [69]. In another experiment, the
Comet (single-cell gel electrophoresis) assay was applied to human lymphocytes in order to
determine the presence of any genotoxic effects of colloidal C
60
fullerenes [70]. The genotox-
icity assay on V79 cells exposed to small diameter SWCNTs (96mgcm
−2
) after 3h of
incubation showed significant DNA damage [71].
The same results (genotoxicity) were observed for WIL2-NS cells exposed to 65 mg mL
−1
TiO
2
nanoparticles for 24h [72]. Carbon black nanoparticles (14nm diameter) at
100 mg mL
−1
showed a significant increase in single-strand DNA breaks, but not double
strand, after 3 h exposure to A549 cells [73]. These nanoparticles, at 75 mg mL
−1
, with the
same scale (295 m
2
g
−1
specific surface area) weakly induced the frequency of mutation in
FE1 Muta
TM
mouse lung epithelial cells. The results demonstrated a significant increase in
DNA strand breaks and oxidized purines by the alkaline Comet assay, both with and
without formamidopyrimidine glycosylase (FPG) [74]. Additionally, diverse nanoparticles
from vehicle exhaust were assessed by the use of a specific tube in the breathing zone dur-
ing bicycling. These nanoparticles influenced mononuclear blood cells and induced
oxidative DNA base damage with no evidence of DNA strand breaks [75]. In another
experiment a water-soluble semiconductor such as CdSe capped with a shell of zinc sulfide
QDs was incubated with double strands of plasmid DNA. After the precipitation
procedure and gel electrophoresis, exposure to the QDs led to DNA damage. DNA isola-
tion from QDs at time 0, which was intended for the plasmid damage assay, demonstrated
instantaneous modification when the QDs and targeted DNA were mixed [76]. The
SWCNTs were prepared from CO and Fe(CO)
5
as the iron-containing catalyst precursor.
Specific analyses by NMAN 5040 (Manual of Analytical Methods, US National Institute
for Occupational Safety and Health) and inductively coupled plasma atomic emission
spectroscopy (ICP-AES) have shown that SWCNTs are comprised of 99.7% (wt) elemental
