Gold nanoparticles

 

 Gold nanoparticles (GNPs) have been shown to greatly increase the efficacy of radiation. Physically, 40-80 keV photons have the highest interaction probability with gold and the best chance to induce an Auger-cascade after undergoing a photoelectric interaction, which leads to a large number (up to ~15) of low energy (Auger and Coster-Kronig) electrons to be released from the gold. Electrons with enough energy to exit a GNP have the potential to cause damage to the nuclear DNA when GNPs are localized in the vicinity of the cellular nucleus. The interaction cross sections for clinically-used megavoltage (MV) photons and protons are orders of magnitudes lower than those for kV photons. However, surprisingly GNP-mediated radiosensitization (GMR) has also been demonstrated for MV photons and even protons.

Macroscopic calculations can not describe the observed effects. Due to the highly localized dose enhancement from GNPs, a single cell will see areas of no dose enhancement at all as well as high dose spikes where the radiation field interacted with a GNP. In order to capture the nanometer-scale effect of GMR, we applied an approach based on the local effect model (LEM) to calculate the biological effects for different GNP distributions in a simplified cell model for various types of radiation modalities. 

In an effort to obtain the most comprehensive description of the GNP effects, we work on refining our approach using track-structure simulations. We simulate the secondary electrons from the incident radiation field as well as those induced by GNPs and their interactions with radiation targets including detailed sub-cellular geometries (nuclear and mitochondrial DNA, cell membranes, etc.). Our goal is to provide a detailed picture of damages at the sub-cellular scale and understand how GNPs increase the effectiveness of radiation in cells, combining track structure Monte Carlo simulations with mechanistic biological modeling of GMR.

Key MGH personnel involved 

  • Jan Schuemann, PhD  (PI)
  • Harald Paganetti, PhD
  • Aimee McNamara, PhD
  • Wonmo Sung, PhD

Collaborators

  • Stephen McMahon (Queens University, Belfast)
  • Jim Hainfeld (Nanoprobes Inc., NY) 

Publications

  1.  Schuemann J, Berbeco R, Chithrani D, Cho S, Kumar R, McMahon S, Sridhar S, and Krishnan S. (2015). Roadmap to clinical use of gold nanoparticles for radiosensitization, Int. J. Rad. Bio. Phys., 94(1), 189-205, *Invited White Paper
  2.   *Lin Y, McMahon SJ, Scarpelli M, Paganetti H, Schuemann J. (2014). Comparing gold nano-particle enhanced radiotherapy with protons, megavoltage photons and kilovoltage photons: a Monte Carlo simulation. Phys. Med. Biol. IOP Publishing;, 59(24), 7675–89. *PMB Highlights of 2014
  3.  Lin YT, McMahon S, Paganetti H and Schuemann J. (2015) “Biological modeling of gold nanoparticle enhanced radiotherapy for proton therapy”, Phys. Med. Biol. 60(10); 4149-4168
  4. Lin Y, Paganetti H, McMahon S, Schuemann J, (2015), Gold Nanoparticle Induced Vasculature Damage in Radiotherapy: Comparing Protons, Megavoltage Photons and Kilovoltage Photons, Medical Physics, 42, 5890. PMC4575320, *Editors Pick
  5. McNamara AL, Kam WWY, Scales N, McMahon SJ, Bennett JW, Byrne HL, Schuemann J, Paganetti H, Banati R and Kuncic Z (2016) “Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol”, Phys. Med. Biol 61(16), 5993.