Biomedical Engineering Reference
In-Depth Information
while maintaining as large as possible the radiosensitizing effect. Thus, efforts
have been made to identify the mechanisms responsible for radiosensitization by
performing X-rays irradiation experiments with specific cell components including
protein [
132
] and supercoiled DNA in solution [
133
-
135
] and high-energy electron
irradiations in UHV with plasmid DNA films [
36
]. The cellular sensitivity to
radiation was expected to be considerably increased by the binding of GNP to DNA,
since the proximity of GNP would cause an increase in the production of short-range
(see Fig.
1.5
) secondary electrons capable of depositing a considerable portion of
their energy into the DNA molecule.
In their efforts to understand DNA damage in the presence of GNP, Foley
et al. [
133
] investigated the indirect effect of radiation (i.e., essentially DNA
damage induced by OH radicals). A solution of supercoiled DNA, bound to GNP
in a GNP:DNA ratio of 100:1 was irradiated by 100 kVp X-rays. The maximum
enhancement in damage was about a factor of two for a dose of 0.5 to 2 Gy, in
good agreement with the dose calculations of Cho [
136
]. Brun et al. [
137
]and
Butterworth et al. [
135
] also investigated damage induced to DNA by OH radicals.
They reported the results of an investigation of four key-parameters governing GNP
radiosensitization of DNA in solution, namely, nature of buffer, DNA:GNP molar
ratio, GNP diameter and incident X-ray energy. Brun et al. performed irradiations
with a clinical source and tested concentration ratios up to 1:1, five sizes of GNP
from 8 to 92 nm and six effective X-ray energies from 14.8 to 70 keV. The most
efficient parameters were large-sized GNP, high molar concentration and 50-keV
photons, which could potentially result in a dose EF of 6. However, the EF decreased
according to the scavenging capacity of the buffers [
135
].
Carter et al. [
134
] developed a Monte Carlo method to investigate the generation
and transport of electrons in plasmid DNA dissolved in water. They chose to model
the small gold nanoparticles (3-nm gold nanoparticles) chemisorbed on DNA. In
the simulation, X-rays from a 100 kVp tungsten source interacted directly with
water and gold. They also probed experimentally the nanoscale spatial profile of
energy deposition created by GNP in aqueous solution with the inclusion of radical
scavengers in the solution to reduce the diffusion distance of hydroxyl radicals, all
the way down to a few nanometers or less from DNA. The resolution afforded by
the scavengers made it possible to characterize the spatial profile of electron energy
deposition of the GNP. The average calculated enhancement of DNA damage due to
GNP caused by hydroxyl radicals was found to be
20
%, which was much lower
than their experimental observation (150%).
The direct effect of radiation (i.e., damage induced directly on DNA by SE
and other secondary products formed from the initial radiation interaction) was
investigated by Zheng et al. [
36
]. Relatively thick (
m) films of
plasmid DNA were bombarded by 60-keV electrons with and without electrostat-
ically bound GNP. SSB and DSB were measured by agarose gel electrophoresis.
The probabilities for formation of SSB and DSB from the exposure of 1:1 and
2:1 gold nanoparticle:plasmid mixtures to fast electrons increased by a factor of
about 2.5 compared to neat DNA samples. For monolayer DNA adsorbed on a thick
gold substrate, the damage per DNA molecule increased by an order of magnitude
0:3
and
2:9
