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

Phys Med Biol. 2014 Nov 7;59(21):6431-43. doi: 10.1088/0031-9155/59/21/6431. Epub 2014 Oct 8.

Abstract

Gold nanoparticles (GNPs) have been shown to sensitize 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 radiosensitization 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. We conclude that GNP generated free radicals are a major cause of radiosensitization and that there is likely to be much less dose enhancement effect with clinical proton beams compared to x-rays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electrons
  • Free Radical Scavengers / therapeutic use*
  • Gold / chemistry*
  • Humans
  • Metal Nanoparticles / therapeutic use*
  • Phantoms, Imaging*
  • Proton Therapy*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / radiotherapy*
  • X-Ray Therapy

Substances

  • Free Radical Scavengers
  • Radiation-Sensitizing Agents
  • Gold