Biomedical Engineering Reference
In-Depth Information
1.7
Gold-nanoparticle enhancement of DNA damage induced
by anti-cancer drugs and radiation
It was shown in Sect.
1.5
that cisplatin increases LEE interactions with DNA and
damage to the molecule, primarily via modification of electron resonances below
15 eV. Since, according to the previous Sect.
1.4
, GNP increase the local density
of LEE, binding GNP to a cisplatin-DNA complex should boost the effect of
cisplatin and further increase DNA damage. This hypothesis was tested by binding
electrostatically GNP to a cisplatin-DNA complex. Dry films of pure plasmid
DNA and DNA-cisplatin, DNA-GNP and DNA-cisplatin-GNP complexes were
bombarded by 60 keV electrons [
143
]. The yields of SSB and DSB were measured
as described in Sect.
1.4
in the experiments of Zheng et al. [
36
] For ratios of GNP
to DNA of 1:1 and cisplatin to DNA of 2:1, the EF of SSB lied between 2-2.5 and
increased to 3 with cisplatin-GNP-plasmid in ratio of 2:1:1. This modest increase
could be only additive and not related to the interaction of the additional LEE on
cisplatin.
For DSB, however, the binding of both GNP and cisplatin to DNA created
a spectacular increase in the EF; i.e., DSB were increased by a factor of 7.5 with
respect to pure DNA
. From the results of the previous section and these EF values, it
appears quite obvious that the additional DSB to the cisplatin-DNA-GNP complex
arises from the generation of additional SE from the GNP. Since the diameter of
DNA is 2 nm, SE from GNP of energy lower than 300 eV, which have an effective
range of about 10 nm [
5
,
33
], (see Fig.
1.5
) could reach up to 10 DNA molecules in
the films. These SE can therefore interact very efficiently with DNA-cisplatin-GNP
complexes.
This synergy observed between GNP and cisplatin in the case of DSB could arise
from a number of basic phenomena. First, we can consider the possibility of two-
event processes triggered by the interaction of a single 60 keV electron with a GNP.
As mentioned in Sect.
1.4
, the yield of DSB is expected to be highly dependent on
two-event processes, such as the damage created by two LEE within the range of
the distance between 10 base pairs
. According to Figs
1.5
and
1.6
, within
10 nm of its site, a single gold atom increases the density of LEE by an average
factor of about 7 in the case of 60 keV electron irradiation. Hence, we expect a
GNP which contains thousands of gold atoms to produce a dramatic increase in this
density. This phenomenon should increase considerably DSB formation by two LEE
interactions on opposite strands within a distance of 10 base pairs. The much higher
EF obtained by combining cisplatin and GNP compared to GNP alone may also
arise in part from the energy requirement to produce a DSB. Since cisplatin locally
modifies the topology of DNA (117,144), the different topology could potentiate
DSB formation. Combined with the electron affinity and chemical reactivity of
cisplatin, these modifications could appreciably lower the energy required to break
two adjacent strands.
Further research is needed to assess the clinical potential of cisplatin-GNP-
DNA complexes and more generally the combination of platinum chemotherapeutic
.4
nm
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