Biomedical Engineering Reference
In-Depth Information
Genotoxicity of Nanomaterials
Several genes are recognized as modulator genes for cell growth or death, and include
c-Myc, p53 and the Bcl-2 family [29]. Apoptosis induction of silver nanoparticles has been
reported as a mitochondria-dependent mechanism, associated by generation of reactive
oxygen species (ROS) and c-Jun N-terminal kinase (JNK) activation [30]. Translocation of
JNK into mitochondria as a result of external stress leads to ROS generation [31, 32]. The
p53 pathway as a mediator for cellular-stress responses is shown to be involved in DNA
repair, senescence, and apoptosis [33]. Nanoparticles can be developed to target p53 for
cell-cycle arrest regulation and growth suppression in tumor cells [34, 35]. Senzer and
co-workers have transported p53 by using a liposomal nanodelivery complex to restore the
normal tumor suppressor gene [36]. Apoptosis induction on cell cultures via the p53
pathway by zinc oxide [37], titanium oxide [38], nickel ferrite [39], silver [40], and tansferrin
and selenium [41] nanoparticles has been reported. B-cell lymphoma 2, encoded by the
Bcl-2 gene, and the Ras family of proteins play essential roles in cell growth and survival
[42, 43]. Activation of JNK, c-Jun, p53, caspase-3 and NF-kappaB, and suppression of
Bcl-2 protein have been observed for human umbilical vein endothelial cells (HUVECs)
during exposure to silica nanoparticles [44]. Nanoparticles can be modified for efficient
delivery of drugs or small interfering RNA (siRNA) into solid tumors to suppress c-Myc
expression and activation of cell apoptosis [45, 46].
Immunotoxicity of Nanomaterials
Preliminary
in vitro
assays for immunotoxicity of nanomaterials include red blood-cell
destruction (hemolysis), platelet aggregation (thrombogenicity), complement activation, and
attraction of macrophages (chemotaxis). Immunity stimulation of nanostructures is deter-
mined by evaluation of antigenicity, adjuvant properties, and inflammatory responses [47].
Stimulation of T-cell CD8/CD4 by polystyrene nanoparticles [48], inflammatory potential of
TiO
2
nanoparticles [49], and low degree of inflammation of carbon nanotubes in the mouse
lung [50] have been reported. From another point of view, polymeric nanoparticles may be
utilized for targeted delivery of anti-inflammatory drugs [51, 52]. In addition, phagocytosis
and nitrogen oxide production by macrophages exposed to the nanostructures may be useful
for studying interactions between the immune system and materials [53]. Nitric oxide (NO)
levels can be determined as a criterion for the activation of macrophages against certain
pathogens.
Surface modifications with polyethylene glycol (PEGylation) or CD 47 are proposed
routes for prevention of opsonization by macrophages [54, 55]. Phagocytosis is the pro-
cess of foreign particle engulfment by cells. Digestion of ingested materials by lysosomes
is facilitated by the formation of superoxide anion, hydrogen peroxide, and ROS.
Therefore, increased ROS levels are correlated by cell activation that results from pathogen
destruction. It has been shown that TiO
2
nanoparticles induce rapid ROS production in
brain-resident macrophages (microglia) [56]. Cobalt and magnesium in the structure of
engineered nanoparticles intensify the formation of oxidative stress [57]. Due to the large
amount of variables in synthesis of nanomaterials and response of living systems,
high-throughput screening is required. In one study, ROS production, mitochondrial
depolarization, and plasma membrane permeability were analyzed, revealing lethal tox-
icity of ZnO in comparison with Pt, Ag, SiO
2
, Al
2
O
3
, and Au particles, which had suble-
thal toxicities [58].
