Biomedical Engineering Reference
In-Depth Information
20.9 INFLAMMATORY RESPONSE AND PHAGOCYTOSIS
Inflammation is an integral part of the immune response. The inflammatory or
in vitro
proinflam-
matory effects of NPs are one of the most widely studied phenomena in nanotoxicological stud-
ies. However, most of these studies reported mainly changes in a few cytokines or chemokines
but lacked mechanistic data. Moreover, NPs can reach distinct body organs after passing through
diverse epithelial or endothelial barriers, which gives particular significance to the evaluation of
their interaction with different types of macrophages and other immune cells. Particular notice must
be paid in evaluating the inflammatory potentials of NPs because various types of NPs (e.g., CB
and TiO
2
) can adsorb proinflammatory mediators. The adsorption of GMCSF, interleukin 6 (IL-6),
and TNF-α on CB (13 nm) and TiO
2
(15 nm) NPs under
in vitro
conditions has been confirmed [19].
Among all the adverse effects caused by NPs, inflammation (a biological reaction of tissues to
harmful stimuli) appears to be the most common factor. Nitric oxide, TNF-α, and IL-8 are key
inflammatory mediators when macrophages are activated. In an interaction between chemically modi-
fied SWCNTs and B lymphocytes, T lymphocytes, and macrophages, it was found that functionalized
SWCNTs were taken up by cells without inducing toxicity [19]. It was observed that only the less
soluble ones preserved lymphocytes' functionality while provoking the secretion of proinflamma-
tory cytokines by macrophages. Strikingly, after CNTs were taken up by murine and rat macrophage
cells, no inflammatory mediators such as NO, TNF-α, and IL-8 were found. However, a dose- and
time-dependent increase of intracellular ROS and a decrease of the mitochondrial membrane poten-
tial occurred. Again, with the purified CNTs, no effect was reported upon incubation. Inflammatory
responses were also observed when human epidermal keratinocytes or human skin fibroblast were
exposed to CNTs. The underlying mechanism may be due to the production of ROS, leading to the
activation of the NF-jB. 30-nm CNTs have the potential to penetrate skin tissue within 2-3 min during
microimaging MRI experiments. Cell adhesion function can be altered by nanotubes [20].
20.10 ANTIGENICITY
Biotechnology-derived pharmaceuticals can cause specific antibody response (antigenicity).
Antibodies are specialized proteins produced by plasma B cells in response to an antigen or foreign
materials. The immune response to a composite NP-based drug potentially involves antibodies for
both the particles and the surface groups. To date, there are very limited studies on the antigenic-
ity of functionalized NPs and none of them report CNT-specific antibody generation. In one study,
CNTs functionalized with a peptide antigen (B cell epitope from the foot-and-mouth disease virus,
FMDV) was examined. The CNT-FMDV was recognized by antibodies equally well as the free
peptide and the immunization of mice with the CNT-FMDV clearly enhanced anti-FMDV peptide
antibody responses. Moreover, no immune response to CNTs was detected, which is an important
issue in view of epitopic suppression when peptide antigen carriers are used [21,22]. A variety of
factors, such as particle surface properties and functional groups, may ultimately affect the systemic
antigenicity of CNTs when it was used as a drug carrier.
20.11 CAUSES OF CARBON NANOPARTICLE IMMUNOTOXICITY
AND CONTROL
Size, shape, structure, and surface all play a role in defining nanotoxicity. The aggregation status
and p-p electronic effects may also be significant in the case of CNTs. CNTs have an unusually
large surface area/mass ratio. The large surface area gives the particles more opportunity to contact
the cellular membrane and proteins, as well as a greater capacity for the absorption and transport of
bioactive substances. The larger surface area also suggests that chemical modification may have a
significant impact on the biological activities of CNTs.
