Biomedical Engineering Reference
In-Depth Information
the surface reactivity of the particles, in influencing the development of inflammatory and cytotoxic
responses in the lung [106].
Surfaces and interfaces of particles are particularly important components of nanoscale mate-
rials. As the particle size is decreased, the proportion of atoms found at the surface is magnified
relative to the proportion inside its volume. This results in nanoscale particle types that are likely to
become more reactive, thus generating more effective catalysts in a variety of applications. However,
when considering the potential health implications, reactive groups on the surface of particles are
also likely to influence the biological (potentially toxicological) effects when compared to nonreac-
tive surfaces or surface coatings. As a consequence, modifications in surface chemistry forming the
“shell” on a (core) NP type may be important and relevant for health effects following exposures.
Moreover, surface coatings can be utilized to alter surface properties of NPs to prevent aggregation
or agglomeration with different particle types. It is interesting to consider the surface coatings, as
it may facilitate NP translocation from the respiratory tract to the systemic circulation and thereby
significantly enhance NPs distribution and exposures to sites throughout the body [41]. It should be
noted that two different NP types containing titanium dioxide as their “core” may not have the same
or even similar hazard potentials. There can be differences in crystal structures (anatase vs. rutile),
surface reactivity, aggregation status, particle size distribution, surface area, as well as surface
coatings—including passivation and neutralization. These differences in physicochemical particle
characteristics despite a similar “core,” may result in comparative differences in the potencies of
pulmonary inflammatory and cytotoxic endpoints [107].
It is necessary to evaluate physicochemical characteristics of NP prior to the initiation of toxi-
cological experimentation. The point cannot be overemphasized that in the absence of an adequate
description of the physicochemical characteristics of the NP type being studied (as well as the
experimental conditions being employed), the results of toxicity experiments with nanoscale materi-
als will have limited value or significance.
19.9
IN VITRO
CYTOTOXICITY TEST
Cu r rently,
in vitro
studies (using established cell lines and primary cells derived from target tissues)
are widely adopted for risk characterization of NPs due to the following reasons: (1)
in vitro
studies
give important information especially in terms of toxic mechanisms, (2)
in vitro
studies enable one
to study the effects of NPs on individual genes, proteins, and other molecules, and (3)
in vitro
stud-
ies facilitate large-scale testing or NPs that are vastly produced to the increasing use of nanomateri-
als in consumer and industrial products.
The first step toward understanding how an agent will react in the body often involves cell cul-
ture studies. Compared to animal studies,
in vitro
studies are less ethically ambiguous, are easier
to control, and are less expensive. In the case of cytotoxicity, it is important to recognize that in
addition to the concentration of the potentially toxic agent being tested, cells in culture are sensitive
to changes in their environment such as fluctuations in temperature, pH, nutrient, and waste concen-
trations. Therefore, controlling the experimental conditions is crucial to ensure that the measured
cell death corresponds to the toxicity of the added NPs versus the unstable culturing conditions. In
addition, as nanomaterials can adsorb dyes and can be redox active, it is important that the choice
of the cytotoxicity assay is appropriate.
19.9.1 c
ell
v
IaBIlIty
t
estINg
Cell viability is the most commonly investigated parameter in cytotoxicity testing. It is important to
perform cell viability studies for each nanomaterial type because of their unique biological response.
It was reported that
in vitro
toxicity of analyzed nanomaterials was not attributed to a defined physi-
cochemical property and the accurate identification of nanomaterial cytotoxicity would require a
matrix based on a set of sensitive cell lines and
in vitro
assays measuring different cytotoxicity
