Biomedical Engineering Reference
In-Depth Information
can develop from various sources, including phagocytic cell response to foreign materials, the pres-
ence of transition metals, insufficient amounts of antioxidants, and the physicochemical properties of
some nanomaterials and environmental factors (Lanone and Boczkowski 2006). The slow clearance
and tissue accumulation (storage) of potential free radical-producing nanomaterials as well as the
prevalence of numerous phagocytic cells in the organs of the reticuloendothelial system (RES) makes
organs such as the liver and spleen the main targets of oxidative stress. In addition, organs of high
blood flow that are exposed to nanomaterials, such as the kidneys and lungs, may also be affected.
Intracellularly, the interaction of nanomaterials with cellular components may occur, which can
potentially disrupt or modify cell functions or lead to the production of reactive oxygen species
(ROS). It may result in oxidative stress, inflammation, and the consequential damage to proteins,
membranes, and DNA. The smaller a particle is, the greater is its surface area-to-volume ratio and
the higher its chemical reactivity and biological activity. The greater chemical activity of nanoma-
terials results in the increased production of ROS, including free radicals. The production of ROS
has been found in a diverse range of nanomaterials, including carbon fullerenes, carbon nanotubes
(CNTs), and metal oxide nanoparticles. The extremely small size of nanomaterials also means that
they much more readily gain entry into the human body than larger-sized particles (Yang et al. 2010,
Chakraborty et al. 2011). Interactions of nanomaterials with the mitochondria and cell nucleus are
being considered as main sources of toxicity. Unfried et al. reviewed that nanomaterials such as
silver-coated gold nanoparticles block copolymer micelles; CNTs and fullerenes may be capable
of localizing to mitochondria and inducing apoptosis and ROS formation, and this nuclear DNA
damage, mutagenesis, cell-cycle arrest, and apoptosis induced by nanomaterials is a possible source
of toxicity (Unfried et al. 2007). Although still under disputation, nanomaterials may be involved
in the upregulation of xanthine oxidase and NADPH oxidase (nicotinamide adenine dinucleotide
phosphate oxidase), which are free radical sources in macrophages and neutrophils (Lanone and
Boczkowski 2006). Other mechanisms of toxicity from nanomaterials should be considered since
nanomaterials immediately interact with their surrounding environments. Once introduced or
absorbed into systemic circulation, their interaction with blood components can result in hemolysis
and thrombosis. Additionally, the interactions of nanomaterials with the immune system have been
known to increase immunotoxicity (Dobrovolskaia and McNeil 2007). In the liver, further meta-
bolic modifications of nanomaterials, for example, by cytochrome P450, may cause hepatotoxicity
by reactive intermediates (Lanone and Boczkowski 2006).
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Endothelial cells (cells that line the vascular system), having very tight junctions typically smaller
than 2 nm, form a physical barrier for particles (Schwab and Pang 2000). Nevertheless, larger val-
ues, from 50 nm (Hussain et al. 2001) up to 100 nm (Schwab and Pang 2000), have been reported
depending on the organ or tissue. A very tight endothelial junction is present in the brain, often
called the blood-brain barrier. However, experiments performed on rats injected with ferritin mac-
romolecules (with sizes around 10 nm) into the cerebrospinal fluid, demonstrated the passage of
ferritin deep into the brain tissue. In certain organs such as the liver, the endothelium is fenestrated
with pores of up to 100 nm, allowing the easier passage of larger particles. In the presence of inflam-
mation, the permeability of the endothelium is increased, allowing a larger passage of particles.
Micro- and nanoparticle debris was detected by scanning electron microscopy in the organs and
blood of patients with orthopedic implants, drug addiction (Gatti and Rivasi 2002), worn dental
prostheses (Ballestri et al. 2001), blood diseases (Gatti et al. 2004), colon cancer, Crohn's disease,
ulcerative colitis (Gatti 2004), and with diseases of unknown etiologies (Gatti and Rivasi 2002).
Coal workers' autopsies revealed an increased amount of particles in the liver and spleen com-
pared to noncoal workers (Donaldson et al. 2005). The pathway of exposure most likely involves
the translocation of the inhaled nanoparticles from the lungs to systemic circulation, followed by
organular uptake.
