Biomedical Engineering Reference
In-Depth Information
Table 10.3 Important recommendations for genotoxicity testing
of nanomaterials
Know what nanomaterial has been tested and in what form
Recognize that nanomaterials are not all the same
Consider uptake and distribution of the nanomaterial
Take nanomaterials specific properties into account
Use standardized methods
Use
in vivo
studies to correlate
in vitro
results
Learn about the mechanism of nanomaterials genotoxic effects
Reprinted with permission from reference [69]. Copyright 2009
Elsevier.
of DNA damage biomarkers as a specific agent for preliminary screening of genotoxicity is
another methodology for nanoparticulated materials. For example, p53 phosphorylation at
serine 15 was increased in the A549 cell lines (adenocarcinoma human alveolar basal epithelial
cells) when the cells were exposed to small-size carbon black nanoparticles (14 nm, printex 90),
whereas no comparable results were detected for a larger size (260 nm) [73]. Table 10.3 lists rec-
ommendations for genotoxicity testing of nanomaterials. However, it should be stated that the
same nanomaterial can produce varying outcomes with different genotoxicity assays.
Reproductive toxicity in a fetus or offspring is considered as an important aspect of material
biocompatibility. For example, injection of silica and TiO
2
nanoparticles into pregnant mice
have been shown to result in smaller sized fetuses. Transportation of nanoscale materials
through the placental barrier leads to neurotoxicity in descendants [82].
Blood Compatibility of Nanomaterials
Alteration in blood components such as plasma residual molecules and blood cells deter-
mines the extent of hemocompatibility of a nanomaterial. Assessments of thrombosis,
coagulation, complement activation, or blood-cell malfunctions should be considered for
interaction between nanomaterials and blood elements. Charge, hydrophobicity, and area
of the contact surface, as well as exposure duration and thermodynamic conditions, all
influence the material-blood interaction. Nanostructures can be engineered as a carrier for
both coagulant and anticoagulant factors. A quantitative measurement of hemoglobin is a
simple way to find the extent of red blood-cell lysis. Ilinskaya and Dobrovolskaia have dis-
cussed interactions between nanoparticles and the coagulation system from the cellular,
biochemical, and hydrodynamic points of view [83]. Different aspects can be considered for
the role of nanoparticle physicochemical properties in interactions with blood components.
For example, a higher degree of hemolysis and inflammation have been observed for smaller
size polystyrene nanoparticles [84]. Minimal interaction with blood cells was noted for
PEGylated negatively charged siRNA-loaded dextran nanogels [85]. Platelet adsorption was
reduced by incorporation of Cu nanoparticles into hydroxyethyl methacrylate [86].
Dendrimers are synthesized as highly branched polymers with a nanosize spherical struc-
ture and numerous functional groups. They can be used independently or as a coating for
other nanostructures in applications such as drug delivery for cancer therapy [87]. Duncan
and Izzo have discussed biocompatibility and blood compatibility related to dendrimer
chemistry in a comprehensive review [88]. Red blood cells, hematocrit, and hemoglobin are
significantly higher for cationic and positively charged dendrimers (NH
2
terminated) in
comparison with anionic ones [89].
