Biomedical Engineering Reference
In-Depth Information
relative to that observed in the
m thick pure DNA films. Most of the energy
of the 60 keV electrons was absorbed by the thick film, whereas for 1-ML DNA
essentially all the energy was absorbed by the gold substrate. Furthermore, as seen
from Fig.
1.5
, LEE have an effective range of about 10 nm; so, in a
2:9
mthick
film, the damage due to any secondary LEE emitted from the gold substrate would
appear in about 0.4% of the total sample. Thus, the increase in damage per DNA
molecule in going from thick to thin films deposited on a gold substrate could be
interpreted as arising from SE whose distribution is shown in Fig.
1.8
.
However, the interaction of a 60 keV electrons with a GNP does not necessarily
produce the same SE energy distribution as that expected from the surface of a
thick gold foil (Fig.
1.8
), which can absorb all of the primary beam [
138
,
139
].
The GNP do not act as a solid for electrons, and the consideration for bulk and
thick foils cannot be applied, unless the GNP have a large diameter. SE have a
probability to be ejected from GNP given by the relativistic M oller cross section
[
138
], which provides the number of collision within the nanoparticle. Furthermore,
any fast charged particle passing near a GNP generates virtual photons that produce
a distribution of SE, consisting mainly of LEE, as explained in the introduction.
Thus, the SE distribution from GNP is expected to be composed essentially of
LEE, whose maximum in the distribution lies at higher energy than that shown in
Fig.
1.8
. In the case of 60 keV electrons, it must also be considered that a single gold
atom has a mass absorption coefficient approximately seven times larger than that
of biological material [
40
] as shown in Fig.
1.6
.
Thus, the results of both GNP-DNA and pure DNA film experiments suggest
that the enhancement of the direct effect of radiation by GNP is principally due to
the production of additional LEE caused by the increased absorption of ionizing
radiation energy by gold, in the form of GNP or a thick gold substrate. Zheng
et al. [
36
] discussed their results in terms of the basic interaction mentioned in
Sect.
1.2
. Since LEE have a range of about five times the diameter of the DNA
helix and they are created in large numbers by any kind of ionizing radiation, the
authors concluded that
the radiosensitizing properties of GNP should be universal
and should exist for any type of high-energy radiation, including the 0.3-20 MeV
photon beams commonly used in radiotherapy
as shown in the animal studies
by Chang et al. [
131
]. Furthermore, since on average only one GNP per DNA
molecule was needed to obtain the sizable increase in damage, the results of Zheng
et al. [
36
] indicated that by targeting GNP to the DNA of cancer cells, these
nanoparticles should be applicable to patients and may thus offer a novel approach
to radiotherapy treatments. In recent cell experiments, GNP were targeted to the
DNA in the nucleus, by linking coded peptides to the gold surface. Interestingly,
a chemotherapeutic effect [
140
] was observed in agreement with further LEE-
impact data on DNA-GNP complexes [
141
] and recent animal studies [
142
]Such
vectorized GNP thus hold promise as chemoradiotherapeutic agents.
2:9
