Biomedical Engineering Reference
In-Depth Information
14.4.3.5 Toxicity of Carbon Nanotubes ................................................................... 305
14.4.3.6 Toxicity of Engineered Nanomaterials ...................................................... 306
14.5 Summary .............................................................................................................................. 306
References ...................................................................................................................................... 306
14.1 INTRODUCTION
Human skin, lungs, and the gastrointestinal tract (GIT) are in constant contact with the environ-
ment. Although the skin is generally an effective barrier to foreign substances, the lungs and the
GIT are more susceptible. These three ways are the most likely points of entry for natural or anthro-
pogenic nanoparticles. Injections and implants are other potential routes of exposure, majorly lim-
ited to engineered materials.
Owing to their small size, nanoparticles can translocate from these entry portals into the circula-
tory and lymphatic systems, and finally to body tissues and organs. Few nanoparticles, depending
on their composition and size, can produce permanent damage to cells by oxidative stress and/or
organelle injuries.
Emphasizing that not all nanoparticles produce adverse health effects—the toxicity of nanopar-
ticles depends on several factors, including their size, aggregation, composition, crystallinity, sur-
face functionalization, and so on. In addition, the toxicity of any nanoparticle to an organism is
determined by the individual's genetic complement, which provides the biochemical toolbox by
which it can adapt to and fight toxic substances. Summarized here are the most extreme adverse
health effects produced by nanoparticles in order to immediately increase the awareness of potential
toxicity of some nanoparticles. Nanoparticles that are introduced into the circulatory system are
associated with the occurrences of arteriosclerosis and blood clots, arrhythmia, heart diseases, and
may finally lead to cardiac death. The translocation of these nanoparticles to other organs, like the
liver and spleen, may lead to the likewise diseases of these organs. A vulnerability to some nanopar-
ticles is related to the occurrence of autoimmune diseases such as systemic lupus erythematosus,
rheumatoid arthritis, and scleroderma (Cristina et al. 2007).
Nanoparticles have been found to be distributed to the liver and spleen after intravenous injec-
tions (El-Ansarty and Al-Daihan 2009). Their distribution is followed by a rapid clearance from
systemic circulation, predominately by the action of liver and splenic macrophages. Processes like
clearance and opsonization, that prepare foreign materials to be more efficiently engulfed by mac-
rophages, occur under certain conditions for nanoparticles depending on their size and surface
characteristics. When inhaled, nanoparticles are found to be distributed to the liver and spleen.
Nanoparticles are cleared from the alveolar region via phagocytosis by macrophages facilitated
by the chemotactic attraction of alveolar macrophages to the deposition site. After oral exposure,
nanoparticles distribute to the kidneys, liver, and spleen. However, some nanoparticles can accumu-
late in the liver during first-pass metabolism.
14.1.1 M
echaNIsMs
of
N
aNoMaterIal
t
oxIcIty
Nanomaterials can modify the physicochemical properties of materials as well as create the oppor-
tunity to increase their uptake and interactions with biological tissues through inhalation, inges-
tion, and injection. A combination of these effects can generate adverse biological effects in living
cells. Nanomaterial toxicity can occur through several different mechanisms in the body. The main
molecular mechanism of
in vivo
nanotoxicity is the induction of oxidative stress by the formation
of free radicals (Lanone and Boczkowski 2006). In excess, free radicals cause damages to biologi-
cal components through the oxidation of lipids, proteins, and DNA. The role of oxidative stress has
been predominant in the induction or the enhancement of inflammation through the upregulation
of redox-sensitive transcription factors such as NF-κB, activator protein-1, and kinases involved in
inflammation (Rahman 2000; Rahman et al. 2005; Lanone and Boczkowski 2006). Free radicals
