Environmental Engineering Reference
In-Depth Information
toxicity of nanoparticles has been reported as in vitro assays (in cell line) and
in vivo (rodents, humans, rabbits and aquatic species, such as zebrafish, catfish,
algae). Giannaccini et al. studied the non-mammalian vertebrate embryos such as
chicken, zebrafish and Xenopus as models for biomedical applications [
3
].
The selection of nanoparticle dose to get accurate therapeutic measure is very
challenging [
4
]. Preclinical, stability assessment in aqueous media, plasma, and
protein adsorption must be analyzed along with purity (indicated by the absence of
lingering contaminants such as antioxidants or homopolymers), reproducibility of
manufacture, and drug release and biodegradability profiles. In the case of metal
nanoparticle, size is mainly determined in dry state while cell line studies are done
in wet condition. It is important that conditions of experiment are the same for
in vivo or in vitro studies and characterization of nanoparticles [
5
].
Quantitative Structure-Activity Relationships (QSAR) can be applied to small
organic compounds with limited applications to nanomaterials. Scientists can take
help of computational molecular methods to predict properties of small molecule up
to large biomolecules, their reactivity and mechanisms of actions. Quantum chem-
ical calculations and molecular dynamics simulations can help to further understand
toxicological aspect. In addition to computational modeling, physiologically based
pharmacokinetic (PBPK) models and modeling dose-response. Mesoscale dynam-
ics (MesoD) techniques can be applied to assess the properties of NPs like molec-
ular volume, surface charges, dipole moment, band gap, transition energies, and
ionization potentials. For structure encoding, various commercial programs such as
DRAGON, CODESSA, CAChe, etc. are used [
6
].
6.3.2 Assays Selection
Toxicity protocol depends very much on the routes of biological exposure. It is
equally important to aware of batch to batch variability of nanoparticles and the
decision on number of batches to be tested. The factors also include reagents and
chemicals used during cell assay, sterility of nanoparticles and cell cultures,
treatment given to cells (exposure time, sonication, temperature (25
C
vs. 37
C)). Safety pharmacology assessment of dextran-coated nanoparticle
graphene at single dose injected intravenously could be predicted in extended
acute toxicity study [
7
]. Mechanism of toxicity is either by accumulation of
nanoparticle at cellular or organ level, resulting in excessive ROS causing oxidative
stress resulting in differences in physiology of cell, cytotoxicity, apoptosis, and
cancer initiation. DNA is a direct target of ROS, results in base and sugar lesions,
DNA eprotein crosslinks and breaks in single- and double-strand. Highly reactive
radicals, such as hydroxyl radicals, can damage DNA quickly in the vicinity.
Superoxide dismutase, peroxidases, and catalases are some of the prominent anti-
oxidant enzymes that efficiently protect against these harmful biological events.
Cell proliferation assay (SRB assay) on optical nanoparticles like gold nanospheres,
gold nanorods, silver nanopheres, silver triangular nanoplates and quantum dots
