Biomedical Engineering Reference
In-Depth Information
them potentially mutagenic or carcinogenic. By the virtue of CNTs being cohesive in nature, they
have a tendency to form stable aggregates, causing inflammatory and oxidative stress at the sites of
their accumulation. These effects, over the course of time, might lead to tissue/organ destruction
and increase the risk of cancer.
Following almost the same fashion as that of asbestos, CNTs are also able to induce cancer and
mesothelioma. Inside biological systems, they stay as stable aggregates in a micron size. Animal
studies have shown that MWCNTs and SWCNTs can induce stress-related inflammatory responses,
reactive oxygen and nitrogen species, and genotoxic effects associated with these effects [27].
Carcinogenic properties of CNTs are coupled with long-term genotoxic stress. CNTs can interact
to cause genotoxicity mainly in two ways: (1) direct interaction with DNA or the mitotic apparatus
and (2) indirectly via oxidative stress and inflammatory response. MWCNTs, due to its long and
thin morphology, are capable of producing asbestos-like toxic responses. There have been interest-
ing studies conducted on intra-abdominal injection of MWCNTs showing mesothelioma-inducing
effects [39]. CNTs are also known to be cytotoxic and cause DNA damage.
20.17 CONCLUSION
Because of the fact that nanotechnological products and nanomedicine research are comparatively
nascent, no standardized guidelines for assessing immunotoxicity due to CNPs are currently avail-
able. Many important issues need to be addressed in order to develop a new generation of nano-
medicines. Available data (Table 20.2) strongly suggest that CNTs upon entering cells cause ROS
TABLE 20.2
Pathophysiology and Toxicity Effects of CNTs
Experimental NM Effects
Possible Pathophysiological Outcomes
ROS generation
a
Protein, DNA, and membrane injury,
a
oxidative stress
b
Oxidative stress
a
Phase II enzyme induction, inlammation,
b
mitochondrial perturbation
a
Mitochondrial perturbation
a
Inner membrane damage,
a
permeability transition (PT) pore opening,
a
energy failure,
a
apoptosis,
a
aponecrosis, cytotoxicity
Inlammation
a
Tissue infiltration with inflammatory cells,
b
ibrosis,
b
granulomas,
b
atherogenesis,
b
acute phase protein expression (e.g., C-reactive
protein)
Uptake by reticuloendothelial system
a
Asymptomatic sequestration and storage in liver,
a
spleen, lymph
nodes,
b
possible organ enlargement and dysfunction
Protein denaturation, degradation
a
Loss of enzyme activity,
a
auto-antigenicity
Nuclear uptake
a
DNA damage, nucleoprotein clumping,
a
autoantigens
Uptake in neuronal tissue
a
Brain and peripheral nervous system injury
Perturbation of phagocytic function,
a
“particle
overload,” mediator release
a
Chronic inlammation,
b
ibrosis,
b
granulomas,
b
interference in
clearance of infectious agents
b
Endothelial dysfunction, effects on blood
clotting
a
Atherogenesis,
a
thrombosis,
a
stroke, myocardial infarction
Generation of neoantigens, breakdown in
immune tolerance
Autoimmunity, adjuvant effects
Altered cell cycle regulation
Proliferation, cell cycle arrest, senescence
DNA damage
Mutagenesis, metaplasia, carcinogenesis
Source:
Table cited at Yu Y. et al.
Nanoscale Research Letters
2008;3:271-7; Table originally from Nel A. et al. Toxic
potential of materials at the nanolevel.
Science
2006;311:622-7. Reprinted with permission of AAAS.
a
Effects supported by limited experimental evidence.
b
Effects supported by limited clinical evidence.
