Gold nanoparticle enhanced proton therapy: A Monte Carlo simulation of the effects of proton energy, nanoparticle size, coating material, and coating thickness on dose and radiolysis yield

Med Phys. 2020 Feb;47(2):651-661. doi: 10.1002/mp.13923. Epub 2019 Dec 2.


Purpose: Radiosensitizer enhanced radiotherapy provides the possibility of improved treatment outcomes by preferentially increasing the effectiveness of radiation within the tumor. Proton therapy offers improved sparing of tissue distal of the tumor along the beam path and reduced integral dose compared to conventional photon therapy. The combination of proton therapy with radiosensitizers offers the potential for an enhanced therapy with increased effect within the tumor and low integral dose. The simulations performed in this work determine the effect of nanoparticle characteristics and proton energy on the nanoscale dose and radiolysis yield enhancement for a single gold nanoparticle irradiated with a proton beam. This data can be used to determine optimal nanoparticle characteristics to enhance proton therapy.

Methods: A two-stage Monte Carlo simulation was performed using Geant4. In the first stage of the simulation, the physical interactions of protons within a gold nanoparticle were modeled and the secondary electrons escaping the nanoparticle's surface were scored in a phase space file. In the second stage of the simulation, the phase space file was used as an input to model the physical interactions of the secondary electrons in water and the resulting production and chemical interactions of reactive species. By comparing a gold nanoparticle with an equivalent water nanoparticle, the nanoscale enhancement of dose and radiolysis yield was calculated.

Results: A large nanoscale enhancement of both the dose and radiolysis yield of up to a factor of 11 due to gold nanoparticles was found for most simulated conditions. For 50 nm gold nanoparticles, a large enhancement factor of 9-11 was observed for high proton energies; however, the enhancement was reduced for proton energies below 10 MeV. For 5 MeV incident protons, it was found that the enhancement factor was approximately 9 for gold nanoparticles of sizes 5-25 nm with a reduction in enhancement observed for nanoparticle sizes outside this range. Additionally, it was found that larger nanoparticle sizes resulted in greater total energy deposition and radiolysis yields per proton flux but with reduced efficiency per nanoparticle mass. It was observed that a large loss of enhancement occurred for thick nanoparticle coatings. However, for polyethylene glycol (PEG) coatings, coating density had a minimal effect on enhancement.

Conclusions: A large enhancement in dose and radiolysis yield was observed. However, the low-energy secondary electrons produced within the gold for lower energy protons are susceptible to self-absorption and result in the loss of enhancement observed for larger nanoparticles and thicker coatings. The radiolysis yield and dose increase with nanoparticle size; however, the yield and dose per gold mass decrease due to self-absorption. Therefore, an intermediate nanoparticle size of approximately 10-25 nm maximizes both the radiolysis yield and dose as well as the enhancement. Coatings should be kept to the minimum effective thickness to limit the loss of enhancement. For molecular coatings such as PEG, coating density should be maximized as this increases the coating's effectiveness with only a minimal effect on enhancement.

Keywords: Monte Carlo; nanoparticles; proton therapy; radiolysis; radiosensitization.

MeSH terms

  • Gold / chemistry*
  • Linear Energy Transfer
  • Metal Nanoparticles / chemistry*
  • Particle Size*
  • Polyethylene Glycols / chemistry
  • Proton Therapy / methods*
  • Pulse Radiolysis
  • Radiation Dosage*
  • Radiotherapy Dosage
  • Silicon Dioxide / chemistry


  • Polyethylene Glycols
  • Gold
  • Silicon Dioxide