Biomedical Engineering Reference
In-Depth Information
unrefined SWCNTs agglomerated and their surface area decreased, and lower surface area resulted
in higher toxicity, whereas refined SWCNTs remained dispersed and thus were less toxic [14].
20.5 NANOPARTICLES RESPONSIBLE FOR TOXICITY
It has been known for some time that NPs are not harmless but can harbor adverse effects. NPs are the
main drivers of proinflammatory effects in cases of particulate matter (PM) toxicity because they are
the main particulate type found in PM mixtures, thus implying that NPs may possess some intrinsic
toxicity. In this context, we should discuss what properties of NP would lead to toxic effects. One
would be the small size of PN as it would lead to a large surface area per unit mass, and particle toxi-
cology can tell that this is often correlated with increased reactivity. Additionally, the larger surface
area also leads to an increased possibility of the formation of free radicals (i.e., superoxide anion or
hydroxyl radicals), which therefore lead to oxidative stress. Thus, this forms the underlying mecha-
nism responsible for the inflammatory responses to carbon nano particles (CNP) exposure. While
the size plays an important role in the toxicity of the particles, the shape of the NP, as well as surface
modifications, can also affect absorption and toxic potential. Another effect of the high surface area
per unit mass of the NP is that it may be responsible for the adsorption of various organic compounds
from air and this phenomenon increases biological interactions within the body. It has been shown by a
number of epidemiological studies that airborne PM from combustion sources such as motor vehicles
or industrial exhaust contributes to morbidity and cardiovascular and respiratory mortality [9].
20.6 CELL UPTAKE OF CARBON NANOPARTICLE
The fact that CNPs can cross the cell membrane had been postulated and observed by several research-
ers. This property of CNPs has enabled their use in drug delivery and gene therapy. To deliver the
drug to the target site, an active molecule must be attached to the delivery device by a covalent or a
noncovalent bond. After reaching the target site, the drug has to enter the specified cell. The process
of internalization can be achieved in two ways: either only the drug can enter the cell alone leaving
the carrier outside or it can enter the cell along with the carrier to initiate the internalization process
for cell uptake of CNPs. Uptake of a drug along with the carried molecule is more efficient as a drug
delivery mechanism because after penetration into the cell, the drug-carrier complex will degrade
releasing the drug inside the cell, whereas in the other internalization process, the extracellular envi-
ronment causes degradation of a drug-carrier conjugate and then the drug penetrates the lipid mem-
brane to enter the cell. The mechanism for cellular uptake of CNTs is not yet entirely understood.
Nevertheless, two ways of internalization have been estimated: (1) through the endocytosis pathway,
and (2) via the endocytosis-independent pathway through passive diffusion across the lipid bilayer
in a needle-like manner. There are five methods to internalize macromolecules or NPs in mamma-
lian cells: phagocytosis (via mannose receptor-, complement receptor-, Fcc receptor-, and scavenger
receptor-mediated pathways), clathrin-mediated endocytosis, macro-pinocytosis, caveolin-mediated
pathways, and clathrin/caveolin-independent endocytosis. Cellular uptake of CNPs is influenced by
its dimensions and surface chemistry and the process is considered to be dose and time dependent
[9]. The mechanism of SWCNT uptake by cell has been shown in Figure 20.5.
20.7 MECHANISM OF CARBON NANOPARTICLE TOXICITY
CNP-exposed cells are subjected to oxidative stress due to the induction of toxic oxidants and
enzymes. An increased level of oxidative stress leads to inflammation and cytotoxicity. Protein
kinase and nuclear factor kappa B (NF-κB) signaling pathways and proinflammatory cytokines
regulate apoptosis in response to oxidative stress. Decreased cell viability and higher levels of the
proinflammatory cytokines interleukin-8 (IL-8) and IL-1β indicate that MWCNTs can initiate an
inflammatory response in human keratinocytes (Heks) at 0.4 mg/mL dose. Apoptosis may result
