Nanodosimetric effects of gold nanoparticles in megavoltage radiation therapy

Background and purpose: The addition of gold nanoparticles (GNPs) to tumours leads to an increase in dose due to their high density and energy absorption coefficient, making it a potential radiosensitiser. However, experiments have observed radiosensitisations significantly larger than the increase in dose alone, including at megavoltage energies where gold's relative energy absorption is lowest. This work investigates whether GNPs create dose inhomogeneities on a sub-cellular scale which combine with non-linear dose dependence of cell survival to be the source of radiosensitisation at megavoltage energies.

Comment on 'Implications on clinical scenario of gold nanoparticle radiosensitization in regards to photon energy, nanoparticle size, concentration and location'

A recent paper by Lechtman et al (2011 Phys. Med. Biol. 56 4631-47) presented Monte Carlo modelling of gold nanoparticle dose modification. In it, they predict that the introduction of gold nanoparticles has the strongest effect with x-rays at kilovoltage energies, and that negligible increases in dose are expected at megavoltage energies. While these results are in agreement with others in the literature (including those produced by our group), the conclusion that '(goldnanoparticle) radiosensitization using a 6 MV photon source is not clinically feasible' appears to conflict with recently published experimental studies which have shown radiosensitization using 6 MV x-ray sources with relatively low gold concentrations. The increasing disparity between theoretical predictions of dose enhancement and experimental results in the field of gold nanoparticle radiosensitization suggests that, while the ability of gold nanoparticles to modify dose within a tumour volume is well understood, the resulting radiosensitization is not simply correlated with this measure. This highlights the need to validate theoretical predictions of this kind against experimental measurements, to ensure that the scenarios and values being modelled are meaningful within a therapeutic context.

Thin-film oxygen sensors using a luminescent polynuclear gold(I) complex

Robust thin-film oxygen sensors were fabricated by encapsulating a lipophilic, polynuclear gold(I) complex, bis{m-(bis(diphenylphosphino)octadecylamine-P,P')}dichlorodigold(I), in oxygen permeable polystyrene and ormosil matrices. Strong phosphorescence, which was quenched by gaseous and dissolved oxygen, was observed from both matrices. The polystyrene encapsulated dye exhibited downward-turning Stern-Volmer plots which were well fitted by a two-site model. The ormosil trapped complex showed linear Stern-Volmer plots for dissolved oxygen quenching but was downward turning for gaseous oxygen. No leaching was observed when the ormosil based sensors were immersed in flowing water over an 8 h period. Both films exhibited fully reversible response and recovery to changing oxygen concentration with rapid response times. (C) 2011 Elsevier B.V. All rights reserved.

An investigation into the effect of thickness of titanium dioxide and gold-silver nanoparticle titanium dioxide composite thin-films on photocatalytic activity and photo-induced oxygen production in a sacrificial system

Thin films of titanium dioxide and titanium dioxide with incorporated gold and silver nanoparticles were deposited onto glass microscope slides, steel and titanium foil coupons by two sol-gel dip-coating methods. The film's photocatalytic activity and ability to evolve oxygen in a sacrificial solution were assessed. It was found that photocatalytic activity increased with film thickness (from 50 to 500 nm thick samples) for the photocatalytic degradation of methylene blue in solution and resazurin redox dye in an intelligent ink dye deposited on the surface. Contrastingly, an optimum film thickness of similar to 200 nm for both composite and pure films of titanium dioxide was found for water oxidation, using persulfate (S2O82-) as a sacrificial electron acceptor. The nanoparticle composite films showed significantly higher activity in oxygen evolution studies compared with plain TiO2 films.

Use of luminescent gold compounds in the design of thin-film oxygen sensors

The use of two gold compounds incorporated into thin plastic films as luminescence quenching oxygen sensors is described. The films are sensitive both to gaseous oxygen and to oxygen dissolved in nonaqueous media such as ethanol. The luminescence quenching of these sensors by oxygen obeys the Stern-Volmer equation and Stern-Volmer constants of 5.35 x 10(-3) and 0.9 x 10(-3) Torr(-1) are found, respectively, for the two dyes in a polystyrene polymer matrix. The sensitivity of the films is strongly influenced by the nature of the polymer matrix, and greatest sensitivity was found in systems based an the polymers polystyrene or cellulose acetate butyrate. Sensitivity was not found to be temperature dependent though raising the temperature hom 15 to 50 degrees C did result in a slight decrease in emission intensity and a hypsochromic shift in the emission wavelength. The rate of response and recovery of the sensors can be increased either by decreasing film thickness or by increasing the operating temperature. The operational and storage stability of these films is generally good though exposure to light should be avoided as one of the dyes tends to undergo photobleaching probably due to a photoinduced ligand substitution reaction.

Gold nanoparticles as novel agents for cancer therapy

Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.

Cell type-dependent uptake, localization, and cytotoxicity of 1.9 nm gold nanoparticles

Background: This follow-up study aims to determine the physical parameters which govern the differential radiosensitization capacity of two tumor cell lines and one immortalized normal cell line to 1.9 nm gold nanoparticles. In addition to comparing the uptake potential, localization, and cytotoxicity of 1.9 nm gold nanoparticles, the current study also draws on comparisons between nanoparticle size and total nanoparticle uptake based on previously published data.

Methods: We quantified gold nanoparticle uptake using atomic emission spectroscopy and imaged intracellular localization by transmission electron microscopy. Cell growth delay and clonogenic assays were used to determine cytotoxicity and radiosensitization potential, respectively. Mechanistic data were obtained by Western blot, flow cytometry, and assays for reactive oxygen species.

Results: Gold nanoparticle uptake was preferentially observed in tumor cells, resulting in an increased expression of cleaved caspase proteins and an accumulation of cells in sub G1 phase. Despite this, gold nanoparticle cytotoxicity remained low, with immortalized normal cells exhibiting an LD50 concentration approximately 14 times higher than tumor cells. The surviving fraction for gold nanoparticle-treated cells at 3 Gy compared with that of untreated control cells indicated a strong dependence on cell type in respect to radiosensitization potential.

Conclusion: Gold nanoparticles were most avidly endocytosed and localized within cytoplasmic vesicles during the first 6 hours of exposure. The lack of significant cytotoxicity in the absence of radiation, and the generation of gold nanoparticle-induced reactive oxygen species provide a potential mechanism for previously reported radiosensitization at megavoltage energies.