Biomedical Engineering Reference
In-Depth Information
CNTs
Resolution of inflammation
Initiation of repair process
Release of anti-inflammatory
cytokines (IL-10, TGF-β)
Genetic damage to
epithelium
Elimination
If no!!
If yes!!
0.36 nm
Phagocytosis
MWCNTs
SWCNTs
1-2 nm
2-25 nm
Proinflammatory response and
activation of phagocytes
Cell internalization
Lymph
node
Respiratory exposure
Shooting of Ca
+2
level and
activation of NFk pathway
Collagen
formation
Fibrosis
Lung deposition
Oxidative stress
Oxyradical generation and
depletion of antioxidants
FIGURE 11.4
(
See color insert.
) Possible pathways following the inhalation of CNTs.
related to the properties of the CNT material, such as their structure, length, surface area, degree
of aggregation, extent of oxidation, bound functional groups, and method of manufacturing (that
can leave the catalytic residues and produced impurities), as well as their dose. Several
in vitro
and
in vivo
studies have inferred that CNTs and/or associated contaminants or catalytic materials that
arise during the production process may induce oxidative stress and prominent pulmonary inflam-
mation. Some studies even suggest comparable similarities between the pathogenic properties of
MWCNTs and those of asbestos fibers [60]. Explorations focused on the elucidation of CNTs toxic-
ity have mainly focused on the pulmonary effects of CNTs administered through the pharyngeal or
intratracheal routes. Several studies demonstrated that both SWCNTs and MWCNTs might induce
cytotoxic effects and apoptosis in different cell types [61-63]. The main reasons behind the toxicity
of CNTs include (i) their nanoparticulate nature; (ii) fiber-shaped architecture and, hence, behavior
like asbestos and other pathogenic fibers, which have toxicities associated with their needle-like
shape; and (iii) they are essentially graphitic and, hence, believed to be biopersistent [64,65].
Muller et al. reported that the agglomerates of intact CNTs remained entrapped in the largest
airway, whereas ground nanotubes were much better dispersed in the lung tissue. CNTs can cause
pulmonary inflammation, fibrosis, stimulate the accumulation of neutrophils and eosinophils, and
increase an assortment of cell-lysing markers in the lungs [66]. These include a significant increase
in total bronchoalveolar lavage cells and polymorphonuclear leukocytes, as well as proteins, lactate
dehydrogenase (LDH), tumor necrosis factor-α, interleukin-1, and mucin levels [67]. In another
breakthrough study, Jacobsen et al. compared the effects of the instillation of three carbonaceous
particles: carbon black, fullerenes C
60
(C
60
), and SWCNTs, as well as gold particles and quantum
dots in mice. Characterizations of the instillation media revealed that all particles were delivered
as aggregates as well as agglomerates. Significant increases in messenger RNA (Mip-2 and Mcp-1)
were detected in lung tissue, 3 and 24 h following the instillation of SWCNTs. The administration
