Biomedical Engineering Reference
In-Depth Information
-Mitochondrial
-Mitochondrial
damage
Nucleus
-DNA damage
Nanoparticles
Plasma membrane
Lysosome
-Physical
damage
-Disruption of cell
membrane
-Oxidative damage
-Surfactant damage
-Damage by toxic ions
Golgi apparatus
-Protein
misfolding
-Protein oxidation
Ve sicle
-Lipid peroxidation
FIGURE 19.1
NP interaction with cells: intracellular targets and nanotoxicological mechanisms. (Reprinted
with permission from Elsaesser A, Vyvyan Howard C. Toxicology of nanoparticles.
Advanced Drug Delivery
Reviews
. 2012;64(2):12-137.)
19.2.3 Np I
NteractIoN
WIth
dNa
During the assessing of nanotoxicological risk caused by nanomaterials, the effect of NPs on DNA
has attracted special attention. The researchers have reported that the NPs are able to enter the
nuclear envelope and result in the possible genotoxic effects of NPs. The genotoxic effects of vari-
ous types of NPs have been investigated [21]. However, these studies have not been able to give
clear direction about the parameter of NPs that is mainly responsible for either positive or negative
outcomes. Also, the mechanism of potential DNA damage is not fully understood. Apart from
direct intercalation or the physical and/or electrochemical interaction with NPs [22], the generation
of reactive oxygen species (ROS) plays a key role in DNA damage. This indicates that particles do
not necessarily reach the nucleus but could induce genotoxicity via oxidative stress [23].
19.3 ENTRY ROUTES OF NPs INTO THE BODY
It has been demonstrated that NPs may gain access to the body via the airways, the skin, or via
ingestion [24,25] (Figure 19.2). The micron-sized particles are largely trapped and cleared by the
upper airway mucociliary escalator system, whereas particles <2.5 μm can get down to the alve-
oli. The deposition of inhaled ultrafine particles (UFPs) (aerodynamic diameter <100 nm) mainly
deposit in the alveolar region [26]. After absorption across the lung epithelium, nanomaterials can
enter the blood and lymph to reach cells in the bone marrow, lymph nodes, spleen, and heart [26]. It
has been proven in cardiovascular events such as coagulation and cardiac rhythm disturbances due
to the association of inhaled ambient UFPs and the heart [27,28]. The ultrafine silver particles were
taken up by alveolar macrophages and aggregated silver particles persisted there for up to 7 days.
