Biomedical Engineering Reference
In-Depth Information
[45], carbon particles, and nanotubes [46,47]. It is well known that asbestos exposure can cause
mesothelioma (cancer of the pleura and peritoneum). Both asbestos fibers and long, multi-walled
carbon nanotubes (CNTs) demonstrates comparable carcinogenic potential. Their similar geometry,
biopersistence (stability in physiological environments), and potential to generate free radicals is
responsible for causing serious tissue damage. The two main physical properties of nanoparticles,
fiber length and biopersistence, were identified as key contributors to toxicity and carcinogenicity
[48]. Kane et al. reported that fibrous materials longer than 10-20 μm undergo incomplete engulf-
ment by macrophages, which “impairs macrophage mediated clearance,” stimulating the release of
free radicals, inflammatory mediators, and growth factors. Fibers of asbestos can also lead to the
aforementioned response, and long-term exposure can cause a constant release of inflammatory
mediators. These free radicals may also cause DNA damage and mutations, favoring tumor devel-
opment and progression [44].
Human exposure to dust containing silicon dioxide, like quartz, can cause pneumoconiosis in
the form of acute or chronic silicosis. It may further lead to the induction of malignant diseases
that may result in obstructive and restrictive lung diseases [47]. One of the most important factors
that determine the lung toxicity of these inhaled nanoparticles is size. Depending on the size, these
particles may deposit at different locations inside the respiratory tract. In general, small particles
(<100 nm) can more efficiently reach distal airways compared with larger particles. Also, small
particles are retained longer than large particles [49]. Apart from size, shape and structure can also
influence inhalation toxicity. Studies have shown that the diameter, length, and surface character-
istics of asbestos fibers dictate their harmful effects [50,51]. For example, a reactive fiber surface
with a small diameter can penetrate deep into the lungs, with the length of the fiber affecting its
elimination [48]. This will determine the development of inflammation, fibrosis, and carcinogenesis
to the affected area in the body [42]. CNTs also exhibit similar pulmonary toxicity because of the
similarity of the aforementioned properties [44].
Inhaled nanoparticles can also cross cell membranes and reach systemic circulation. These par-
ticles can then penetrate and deposit into other organs, such as the liver, spleen, kidneys, heart, and
brain, and can produce toxic effects to these vital organs. These particles can induce inflammatory
and prothrombotic responses, and can cause atherosclerosis and thrombogenesis. Inside the brain,
these deposited particles can cause neurotoxicity and neurodegenerative diseases. Studies provide
evidence that these particles translocate to various vital organs, producing serious, unwanted, toxic
effects [52,53].
Nanoparticles, once cleared from the respiratory tract, can be ingested into the gastrointestinal
(GI) tract [54]. They can also be ingested directly into the GI tract with food, water, drugs, or drug
delivery devices [55]. The effect of nanoparticles on the GI system has not been extensively studied.
Only a few studies have examined the effects of ingested nanoparticles [42]. Zhen et al. studied the
toxicity of copper nanoparticles (23.5 nm) and micro copper particles (17 μm)
in vivo
. The copper
particles were administered in mice via oral gavage and LD50 was found to be 41 mg/kg for copper
nanoparticles compared with >5000 mg/kg for micro copper particles. The copper nanoparticles
produced serious injuries to the liver, kidneys, and spleen [56]. Yamago et al. [57] showed that
water-soluble fullerenes, upon oral administration in rats, were not efficiently absorbed, and were
primarily excreted in the feces.
The skin, as the largest defense barrier consisting of three layers—the epidermis, dermis, and the
subcutaneous layer—plays a very important role in determining the cytotoxic effects of nanomateri-
als by impeding their permeation. The keratinized
stratum corneum
of the epidermis layer is one
of the most important components of the tight mechanical barrier, as it significantly restricts per-
meation of foreign materials. However, skin structures such as hair follicles, sebaceous glands, and
sweat glands may act as reservoirs and potentials routes of penetration, with the potential for thera-
peutic and drug delivery applications or toxicological effects [58]. Once the nanomaterials have
penetrated the top keratinous layers of the skin, possible phagocytosis by macrophages, Langerhans
cells, and keratinocytes may occur, potentially triggering the immune system [59,60]. Although
