Gold Nanoparticles as Radiation Sensitizers in Cancer Therapy

Abstract

Among other nanoparticle systems, gold nanoparticles have been explored as radiosensitizers. While most of the research in this area has focused on either gold nanoparticles with diameters of less than 2 nm or particles with micrometer dimensions, it has been shown that nanoparticles 50 nm in diameter have the highest cellular uptake. We present the results of in vitro studies that focus on the radiosensitization properties of nanoparticles in the size range from 14-74 nm. Radiosensitization was dependent on the number of gold nanoparticles internalized within the cells. Gold nanoparticles 50-nm in diameter showed the highest radiosensitization enhancement factor (REF) (1.43 at 220 kVp) compared to gold nanoparticles of 14 and 74 nm (1.20 and 1.26, respectively). Using 50-nm gold nanoparticles, the REF for lower- (105 kVp) and higher- (6 MVp) energy photons was 1.66 and 1.17, respectively. DNA double-strand breaks were quantified using radiation-induced foci of gamma-H2AX and 53BP1, and a modest increase in the number of foci per nucleus was observed in irradiated cell populations with internalized gold nanoparticles. The outcome of this research will enable the optimization of gold nanoparticle-based sensitizers for use in therapy.

Evaluation of cytotoxicity and radiation enhancement using 1.9 nm gold particles: potential application for cancer therapy

“…Gold nanoparticles have been shown as potential radiation enhancing agents for the treatment of cancer [21][22][23][24][25]. This was first demonstrated by Hainfeld et al [21] who obtained dose enhancement ratios of at least 2, but potentially as high as 6 using 1.9 nm particles at a gold concentration of 7 mg g −1 when administered by intravenous injection to tumourbearing mice irradiated with 250 kVp x-rays.…”

“…The effect of different sized nanoparticles (14-74 nm) was recently shown [25] with 50 nm particles showing the highest enhancement factor of 1.66 when irradiated with 6 MVp photons.…”

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

“…Across the nanoparticle compositions studied, GNPs show the highest potential to increase the radiosensitivity of cells. [3][4][5] A dose enhancement from using GNPs in radiotherapy has already been demonstrated using Monte Carlo simulations; 6 however these simulations are of limited accuracy at micrometer scales, as the continuous physics models used to date break down at small spatial resolutions. 7,8 As one moves towards more accurate microdosimetric measurements of the impact of GNPs, discrete physics models become necessary as they improve the spatial resolution in simulation.…”

Radiosensitising Nanoparticles as Novel Cancer Therapeutics — Pipe Dream or Realistic Prospect?

“…Although a maximum radiosensitising effect was found for cells irradiated with 105 kVp X-rays in the presence of 760 μg/mL GNPs, a DEF of 1.17 ± 0.02 was reported in combination with unmodified LINAC-generated 6 MV X-rays (43). This result is in clear disagreement with a theoretically predicted value of 1.008, again highlighting the complex nature of nanoparticle-induced radiosensitisation and the need to consider the shower spectrum (11).…”

“…These finding appear to contradict the physical similarities between the mass energy absorption coefficients of gold and soft tissue using MV radiation sources. Despite this numerous groups have reported significant DEFs using clinical radiation sources delivering MV X-rays (5,(43)(44)(45). The data presented by…”