Biomedical Engineering Reference
In-Depth Information
longer than 24 h (Doak et al. 2009). Moreover, treatments should be long enough to ensure the
access of the NPs to the nucleus during mitosis (Gonzalez et al. 2011).
The susceptibility of different cell lines and different animal models to NPs has not yet been
thoroughly studied. Paino et al. (2012) found that peripheral blood mononuclear cells were less sen-
sitive to Au NP-induced DNA damage than were HepG2 (human cells derived from hepatocellular
carcinoma). Nielsen et al. (2008) found differences in the sensitivity of two strains of mice while
Kim et al. (2008) found differences in the accumulation of silver NPs in female and male kidneys.
The susceptibility of organs can be due to differences in their metabolic rate, antioxidant defense,
and DNA repair capability.
The different exposure routes used in
in vivo
experiments affects the NPs biodistribution and
would give different genotoxic profiles in different organs. The clearance also depends on the route
of administration (Nielsen et al. 2008).
Dispersion methods used to prepare the NPs (e.g., sonication or vortexing) can influence the
results of genotoxicity studies; NP aggregates and agglomerates may complicate the interpretation
of the results (Pfaller et al. 2010). Magdolenova et al. (2012) suggested that at least two different
dispersion procedures should be used. Moreover, the solvent can affect the stability of the NPs
(Pfaller et al. 2010).
Merhi et al. (2012) confirm the importance of serum and proteins in cell culture medium; the
presence of serum partially protects the cells from the genotoxicity induced by positively charged
NPs by decreasing their cellular uptake.
17.7 CHARACTERISTICS OF NPs THAT INFLUENCE POTENTIAL
GENOTOXICITY
It has been demonstrated that some characteristics of NPs have a great impact on their genotoxic-
ity, mainly because they modify biokinetics (Nel et al. 2006; Singh and Nalwa 2007; Gratton et al.
2008). Chemical composition, particle size, shape, surface charge, and coating can vary, among
other characteristics.
The different chemical composition obviously influences the genotoxicity of NPs. Moreover, it
has been demonstrated that different crystalline structures also change the genotoxic potential of
NPs with the same chemical composition (Petkovic et al. 2011).
Many studies have demonstrated that small NPs exert more DNA damage than bigger ones, both
in vitro
and
in vivo
(Konczol et al. 2011; Park et al. 2011a,b; Downs et al. 2012; Jugan et al. 2012).
It seems clear that small NPs can be taken up by the cells more easily, but some authors claim that
larger NPs would penetrate the cell membrane more easily by endocytosis than smaller NPs (Hong
et al. 2011). These large NPs would be present in vacuoles inside the cell, reducing their accessibility
to the nucleus.
The surface properties of NPs give them the possibility to form aggregates. The stability of
these agglomerates, or the NP
per se
, in the cell culture medium or body fluids and tissues will
affect the biokinetics of the NPs (Doak et al. 2009). A positive correlation between DNA damage
and positively charged NPs has been observed (Hong et al. 2011; Shah et al. 2012). Hong et al.
(2011) found that positively charged, coated NPs seemed to be more concentrated inside the cell
than NPs with negatively charged coatings. Coatings can have different functions depending on the
coating material; its effects can cause or prevent extensive agglomeration of the NPs, or can protect
or induce the interaction of NPs with cells or biomolecules. All these options have an impact on
the genotoxic potential (Yin et al. 2010; Toyooka et al. 2012). Moreover, NPs can absorb organic
molecules and macromolecules onto their surface, influencing the results of
in vitro
studies (Doak
et al. 2009).
The shape can also affect the specific physicochemical and transport properties and, thus, the
genotoxicity (Yang et al. 2009). It seems that materials with a high aspect ratio have a higher inter-
nalization rate and more of an impact on cellular functions than their low-aspect-ratio counterparts
