Biomedical Engineering Reference
In-Depth Information
The contact between cells and NPs is believed to induce the formation of
reactive oxygen species (ROS) cellular signaling cascades that control cellular
proliferation, inflammatory processes, and cell death [
86
]. Oxidative stress is
caused by an unbalance between the production of reactive oxygen and a biological
system's ability to readily detoxify the reactive intermediates or easily repair the
resulting damage. All forms of life maintain a reducing environment within their
cells. Enzymes that maintain the reduced state through a constant input of metabolic
energy preserve this reducing environment. Disturbances in this normal redox state
can cause toxic effects through the production of peroxides and free radicals that
damage all components of the cell, including proteins, lipids, and DNA.
The main cellular substructures affected are the following:
(1) The plasma membrane with enzyme complexes such as the NADPH oxidases,
(nicotinamide adenine dinucleotide phosphate-oxidases), the activity and regu-
lation of which may be affected by interaction with nano-sized particles
(2) The mitochondria electron flow and leakage from the inner membrane
(3) The endoplasmic reticulum's calcium ion levels may be disregulated
The production of ROS by NPs is dependent on the chemical reactivity of
nanoparticle materials, the chemical reactivity of impurities found in particle
preparations, and the physical interaction of particles with cellular structures
involved in the catalysis of biological reduction-oxidation process.
In vitro and in vivo studies have shown that among particles of different sizes,
nanoparticles which have a size smaller than 100 nm are potentially the most
dangerous due to their large surface area, deep penetration, and high content of
reduction-oxidation cycling organic chemicals [
87
]. Moreover, it has been
demonstrated that carbon nanotubes hinder macrophages ability to degrade and
remove foreign particles. Macrophages are believed to being incapable of
incorporating long and stiff nanotubes into their phagosomes. Oxygen radicals
and hydrolytic enzymes are excreted in the microenvironment in an effort to
obliterate the CNTs, thus leading to chronic inflammation. This chronic inflamma-
tion could lead over time to mutagenesis, a problem previously encountered with
asbestos fibers.
Although oxidative stress is involved in many diseases, such as atherosclerosis,
Parkinson's disease, myocardial infarction, and Alzheimer's disease, ROS are not
automatically harmful. It is only when the protective responses fail to provide
adequate protection that a further increase in ROS production can result in
proinflammatory and cytotoxic effects. The presence of immune system proteins
and cells, such as proinflammatory cytokines (IL-1, IL-6, and TNF-
α
), Th1-type
cytokines (IL-12 and IFN-
), Th2-type cytokines (IL-4, IL-5, and IL-10),
macrophages, and neutrophils, is indicative of an inflammatory response. Although
little is known about the physicochemical factors that provoke an inflammatory
response and apoptosis subsequent to NP exposure, it is believed that NP size is a
determining factor. Size-dependent effects of nanomaterials have been observed in
instillation and inhalation exposure studies where the inflammatory responses of
experimental animals correlated specifically with nanoparticle surface area [
88
-
90
].
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