Biomedical Engineering Reference
In-Depth Information
resulting in free radical formation, further increasing the inflammatory response [119,120,123].
The generation of ROS and inflammation may further result in mitochondrial damage and apop-
tosis [124]. In the case that oxidative stress overwhelms the cell's capacity to restore the redox
balance, it may lead to cell death by necrosis, apoptosis, and adaptive proinflammatory responses.
Repair processes and antioxidant enzymes may be activated. These cellular responses are usually
targeted in the design of cancer treatments, making nanomaterials attractive in drug development
and delivery. However, the scope of inflammatory action depends on the type of the nanomaterial
and its physiochemical properties.
The interactions of nanoparticles, activation of inflammatory responses, and modulation of path-
ways may facilitate a pathological process but could also be utilized to achieve therapeutic goals.
Some nanoparticles, such as fullerenes investigated by Lao et al. in fact have the capacity to attenu-
ate the effects of oxidative stress and reduce mitochondrial swelling, characteristic of apoptosis
[125]. Thus, specific biointeractions are more dependent on the interplay of multiple factors relating
to nanoparticle makeup and surface properties, the characteristics of the suspending media, the
properties of nanoparticle-media interface, and the nano-bio interface of the nanoparticle and its
shell with the cell membrane and its proteins and receptors [89].
9.2.4 d esIgN B Iosafety
Nanotoxicology is a very broad discipline. With a countless number of combinations and variables,
it may seem like a daunting task to account for all of the factors at play. Additional factors play a
role, such as the difficulty in determining the effective dose for a toxicology treatment, as a very
high dose might not have a physiological significance. Thus, it is very important that the optimal
dose is determined in a gradient, and not simply the highest dose to get the desired results [126-
129]. Furthermore, in vivo experimental data might be difficult to extrapolate into human applica-
tions, as the animal model might not necessarily provide an adequate analog. How is it best to go
about the design and toxicology testing of nanomaterials?
Designing nanoparticle delivery systems is somewhat similar to a Rubik's cube puzzle. Although
there are multiple parameters that can be specified, victory lies in the selection of the appropriate
characteristics for targeting specific actions and localizations in the body. As the large surface area
of the nanoparticle determines most of its properties, understanding the biointeractions at the sur-
face becomes crucial. The selection of material plays a crucial role, yet, even nontoxic substances
may possess toxicity in the form of a nanoparticle. Thus, through the manipulation of the nanopar-
ticle surface, biocompatibility can be secured. Coating the nanoparticle with biocompatible material
could help manage cytotoxicity and regulate cell uptake [89]. Furthermore, coating of the nanopar-
ticle would offer control over the composition of proteins in the corona by steric hindrance. So far,
the focus has been on the cytotoxicity of the nanoparticle; however, the nanoparticle may carry toxic
compounds either by design, such as API, or through the manufacturing process—DMSO, and so
on [130,131]. The stability of the coatings would be crucial in ensuring biocompatibility and the
containment of toxic cargo. Appropriate shells could be either biocompatible organic or inorganic
substances, such as PEG, PEG-SiO 2 , gold, and biocompatible polymers [132].
Decreasing hydrophobicity and modulating the surface charge is another aspect that would allow
for the attenuation of cytotoxicity by decreasing the adverse interactions with proteins, such as a
strong, irreversible binding, a change of confirmation, a loss of activity, and fibrillation [92,133].
Agglomeration is another aspect that could help lower protein binding and the number of biointerac-
tions. Further, adjusting the surface charge can help regulate cell uptake. For example, a layer-by-
layer polyelectrolyte coating allows control over the rate of cell uptake, surface charge, and surface
functionality [93]. Furthermore, functionalizations with hydrophilic groups can be used to increase
urinary excretion rates as an additional safety measure to prevent the accumulation of potentially
toxic materials [134,135]. It has also been postulated that an increase in nanomaterial solubility
might lower the production of ROS and decrease their toxicity.
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