Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

Abstract

Gold nanoparticles (GNPs) have been shown to sensitise cancer cells to X-ray radiation, particularly at kV energies where photoelectric interactions dominate and the high atomic number of gold makes a large difference to X-ray absorption. Protons have a high cross-section for gold at a large range of relevant clinical energies, and so potentially could be used with GNPs for increased therapeutic effect.Here, we investigate the contribution of secondary electron emission to cancer cell radiosensitisation and investigate how this parameter is affected by proton energy and a free radical scavenger. We simulate the emission from a realistic cell phantom containing GNPs after traversal by protons and X-rays with different energies. We find that with a range of proton energies (1 -250 MeV) there is a small increase in secondaries compared to a much larger increase with X-rays. Secondary electrons are known to produce toxic free radicals. Using a cancer cell line in vitro we find that a free radical scavenger has no protective effect on cells containing GNPs irradiated with 3 MeV protons, while it does protect against cells irradiated with X-rays.3

Metallic nanoparticles irradiated by low‐energy protons for radiation therapy: Are there significant physical effects to enhance the dose delivery?

“…19 Jeynes et al used a low-energy proton beam to irradiate bladder carcinoma cells loaded with 50 nm Au-NPs, but no enhancement of cell killing was observed. 20 In contrast, our recent study using lung cancer cells showed sensitization when 25 keV/lm protons were used, but not with 10 keV/lm protons in combination with 10 nm Au-NPs. 21 Additionally, exposure to heavier ions seems to provide a marked sensitization effect.…”

Modelling direct DNA damage for gold nanoparticle enhanced proton therapy

“…They found an ER of 1.22-1.43 at 2 Gy for the 1.3 MeV beam depending on the GNP size, but no significant enhancement for the 4 MeV beam. Similarly, Jeynes et al 17 did not see any radiosensitization effect when RT-112 bladder cancer cells were irradiated with 3 MeV protons, although their result may be an outcome of the relatively low GNP concentration used. In spite of the experimental validation of GNP enhanced proton therapy, computational models have suggested a much lower radiosensitization effect.…”

Actual questions raised by nanoparticle radiosensitization

“…No clear effect has been seen with protons of 3 MeV and 6 or 50 nm gold NP (Jeynes et al, 2014;Liu et al, 2010) though others publications evoke the beneficial proton-NP combination. For iron NP, Kim obtained a 20-28% increase of cell death with 14 nm FeNP and 45 MeV proton but also with 2 nm and 13 nm gold NP (Kim et al, 2010).…”