Chemistry Reference
In-Depth Information
such as accuracy, invasive needle placement, and toxic effects, on the tissue
surrounding the tumor and also on internal organs [
190
,
191
]. These side effects
have a drastic limitation on the amount of radiation used during treatment.
Several studies have focused on the use of AuNPs as novel high-Z radiosen-
sitizing agent to increase the sensitivity of tumors irradiated with clinical X-ray
beams [
192
,
193
]. Numerous experimental [
194
-
196
] and theoretical studies
[
197
-
199
] have shown that clinically significant enhancements are achievable
with AuNPs-treated tumors in combination with X-ray therapy.
In vitro studies showed AuNP radiosensitization by irradiation of cells and
plasmid DNA [
200
-
204
]. Irradiating plasmid DNA in the presence of 5 nm
AuNPs leads to single-strand and double-strand break enhancement [
202
]. Rahman
et al. observed a biological dose enhancement factor of up to 24.6 when irradiating
bovine aortic endothelial cells in the presence of 1.9 nm AuNPs [
203
]. Roa
et al. were the first who reported that 10.8 nm glucose-capped AuNPs trigger the
activation of CDK kinases leading to cell cycle accumulation in the G2/M phase
and acceleration in the G0/G1 phase [
205
]. This leads to the suggestion that p53 and
the CDK kinases are targets for AuNPs. A striking sensitization to ionizing radia-
tion is achieved as well. In another study AuNPs with an approximate size of 45 nm
showed an increase of the effectiveness of proton radiotherapy for the killing of
prostate tumor cells of about 15-20% [
206
].
Despite the rapid increase of in vivo studies investigating the uptake and
distribution of AuNPs, there remains a lack of studies of in vivo radiosensitization
with these particles. In 2004, the suitability of AuNPs for radiotherapy was exam-
ined by Hainfeld et al. in vivo [
192
]. Nontargeted 1.9 nm AuNPs (AuroVist) in
combination with 250 kV radiation were shown to prolong survival in Balb/C mice
bearing EMT-6 murine breast cancer tumors. One month after the treatment, a
dramatic reduction in tumor growth was observed. Based on these results, a second
experiment with a longer follow-up study in mice which received a slightly lower
radiation dose alone or with AuNPs was pursued. A remarkable tumor regression in
mammary tumors and long-term survival without any significant toxicity were
demonstrated thus indicating the utility of these particles for radiotherapy. In a
recent study by Hainfeld et al., a highly radioresistant murine squamous cell
carcinoma was used in mice [
207
]. A significant tumor growth delay and a long-
term tumor control were observed by combining AuNPs with irradiation. Chang
et al. used 13 nm citrate-stabilized AuNPs in a mouse model with B16F10 murine
melanoma cells. A significant in vivo tumor growth delay and increased survival
were noted when AuNPs were injected 24 h before irradiation [
195
]. The median
survival of the mice with 65 days was shorter than in the Hainfeld study but the
AuNP concentration used is much lower.
While demonstrating the potential efficacy of AuNP radiosensitization, the large
variations in these studies revealed AuNP radiosensitization to be highly sensitive
to a number of physics and pharmacological parameters such as irradiation energy,
AuNP size and concentration, and intracellular localization [
192
,
202
,
203
]. Toward
understanding and predicting the effects of these parameters, there have been a
number of Monte Carlo simulation studies exploring AuNP dose enhancement
[
197
,
198
,
208
-
213
].
