Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

Recent progress in Monte Carlo simulation on gold nanoparticle radiosensitization

1 Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
2 Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

Special Issues: New horizons for computer simulation in biology

Gold nanoparticles (GNPs) are proven effective heavy-atom radiosensitizers to produce imaging contrast and dose enhancement in radiotherapy. To understand the physical and biological effect of adding GNPs to the tumour cells, Monte Carlo simulation based on particle tracking and transport, is employed to predict the dosimetry in the cellular and DNA scale. In this review, we first explore the recent advances in Monte Carlo simulation on GNP radiosensitisation. The development of particle tracking algorithm for very low energy electron in the simulation is discussed, followed by some results regarding the prediction of dose enhancement (microscopic and macroscopic). We then review different Monte Carlo cell models with GNPs in the simulation, the biological effect resulting from DNA damage, and the effects of increasing imaging contrast in the tumour cell due to photoelectric enhancement. Moreover, we explain and look at different studies and results on GNP-enhanced radiotherapy using gamma rays (brachytherapy), megavoltage photon, kilovoltage photon, electron and proton beams.
  Article Metrics

Keywords gold nanoparticle; Monte Carlo simulation; radiotherapy; dose enhancement; imaging contrast enhancement

Citation: James C. L. Chow. Recent progress in Monte Carlo simulation on gold nanoparticle radiosensitization. AIMS Biophysics, 2018, 5(4): 231-244. doi: 10.3934/biophy.2018.4.231


  • 1. Citrin DE (2017) Recent developments in radiotherapy. N Engl J Med 377: 1065–1075.    
  • 2. Hanna P, Shafiq J, Delaney GP, et al. (2017) The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits. Radiother Oncol 126: 191–197.
  • 3. Zubizarreta E, Van DJ, Lievens Y (2016) Analysis of global radiotherapy needs and costs by geographic region and income level. Clin Oncol 29: 84–92.
  • 4. Deloch L, Derer A, Hartmann J, et al. (2016) Modern radiotherapy concepts and the impact of radiation on immune activation. Front Oncol 6: 141.
  • 5. Baskar R, Dai J, Wenlong N, et al. (2014) Biological response of cancer cells to radiation treatment. Front Mol Biosci 1: 24.
  • 6. Awwad HK (1990) The Overall Radiobiological Effect: The Evolution of Radiation Damage, In: Radiation Oncology: Radiobiological and Physiological Perspectives, Developments in Oncology, Springer, Dordrecht, 3–15.
  • 7. Mcmillian TJ, Tobi S, Mateos S, et al. (2001) The use of DNA double-strand break quantification in radiotherapy. Int J Radiat Oncol Biol Phys 49: 373–377.    
  • 8. Chow JCL (2017) Dose Enhancement Effect in Radiotherapy: Adding Gold Nanoparticle to Tumour in Cancer Treatment. Nanostruct Cancer Ther 2017: 383–400.
  • 9. Hanks GE, Hanlon AL, Schultheiss TE, et al. (1998) Dose escalation with 3D conformal treatment: Five-year outcomes, treatment optimization, and future directions. Int J Radiat Oncol Biol Phys 41: 501–510.    
  • 10. Purdy JA (1996) Volume and dose specification, treatment evaluation, and reporting for 3D conformal radiation therapy, In: Palta J, Mackie TR, eds. Teletherapy: Present and Future, College Park, Md, Advanced Medical Publishing, 235–251..
  • 11. Perez CA, Purdy JA, Harms WB, et al. (1995) Three-dimensional treatment planning and conformal radiation therapy: Preliminary evaluation. Radiother Oncol 36: 32–43.    
  • 12. Mesbahi A (2010) A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer. Rep Pract Oncol Radiother 15: 176–180.    
  • 13. Ghita M, Mcmahon SJ, Laura E (2017) A mechanistic study of gold nanoparticle radiosensitisation using targeted microbeam irradiation. Sci Rep 7: 44752.    
  • 14. Haume K, Rosa S, Grellet S, et al. (2016) Gold nanoparticles for cancer radiotherapy: A review. Cancer Nanotechnol 7: 8.    
  • 15. Mcmachon SJ, Hyland WB, Muir MF, et al. (2011) Nanodosimetric effects of gold nanoparticles in megavoltage radiation therapy. Radiother Oncol 100: 412–416.    
  • 16. Cui L, Her S, Borst GR, et al. (2017) Radiosensitization by gold nanoparticles: Will they ever make it to the clinic? Radiother Oncol 124: 344–356.    
  • 17. Her S, Jaffray DA, Allen C (2017) Gold nanoparticles for applications in cancer radiotherapy: Mechanisms and recent advancements. Adv Drug Deliv Rev 109: 84–101.    
  • 18. Chithrani DB, Jelveh S, Jalali F, et al. (2010) Gold nanoparticles as radiation sensitizers in cancer therapy. Radiat Res 173: 719–728.    
  • 19. Chow JCL (2017) Application of Nanoparticle Materials in Radiation Therapy, In: Leticia Myriam Torres Martinez, Oxana Vasilievna Kharissova and Boris Ildusovich Kharisov (Eds.), Handbook of Ecomaterials, Springer Nature, Switzerland.
  • 20. Chow JCL (2016) Photon and electron interactions with gold nanoparticles: A Monte Carlo study on gold nanoparticle-enhanced radiotherapy. Nanobiomater Med Imaging 8: 45–70.
  • 21. Chow JCL (2015) Characteristics of secondary electrons from irradiated gold nanoparticle in radiotherapy, In: Mahmood Aliofkhazraei (Ed.), Handbook of nanoparticles, Springer International Publishing, Switzerland, Chapter 10, 41–65.
  • 22. Chow JCL (2018) Monte Carlo nanodosimetry in gold nanoparticle-enhanced radiotherapy, In: Maria F. Chan (Ed.), Recent advancements and applications in dosimetry, New York: Nova Science Publishers. Chapter 2.
  • 23. Yamada M, Foote M, Prow TW (2015) Therapeutic gold, silver, and platinum nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 7: 428–445.    
  • 24. Jeynes JC, Merchant MJ, Spindler A, et al. (2014) Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies. Phys Med Biol 59: 6431–6443.    
  • 25. Hainfeld JF, Dilmanian FA, Zhong Z, et al. (2010) Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma. Phys Med Biol 55: 3045–3059.    
  • 26. Hainfeld JF, Smilowitz HM, O'Conor MJ, et al. (2013) Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine 8: 1601–1609.    
  • 27. Daniel MC, Astruc D (2004) Gold nanoparticles: Assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 104: 293–346.    
  • 28. Saha K, Agasti SS, Kim C, et al. (2012) Gold nanoparticles in chemical and biological sensing. Chem Rev 112: 2739–2779.    
  • 29. Giljohann DA, Seferos DS, Daniel WL, et al. (2010) Gold nanoparticles for biology and medicine. Angew Chem 49: 3280–3294.    
  • 30. Jans H, Huo Q (2012) Gold nanoparticle-enabled biological and chemical detection and analysis. Chem Soc Rev 41: 2849–2866.    
  • 31. Murphy CJ, Gole AM, Stone JW, et al. (2008) Gold nanoparticles in biology: Beyond toxicity to cellular imaging. Acc Chem Res 41: 1721–1730.    
  • 32. Jain S, Hirst DG, O'sullivan JM (2012) Gold nanoparticles as novel agents for cancer therapy. Br J Radiol 85: 101–113.    
  • 33. Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6: 662–668.    
  • 34. Grzelczak M, Pérez-Juste J, Mulvaney P, et al. (2008) Shape control in gold nanoparticle synthesis. Chem Soc Rev 37: 1783–1791.    
  • 35. Lechtman E, Chattopadhyay N, Cai Z, et al. (2011) Implications on clinical scenario of gold nanoparticle radiosensitization in regards to photon energy, nanoparticle size, concentration and location. Phys Med Biol 56: 4631.    
  • 36. Jiang W, Kim BY, Rutka JT, et al. (2008) Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol 3: 145.    
  • 37. Albanese A, Tang PS, Chan WC (2012) The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 14: 1–6.    
  • 38. Binder K, Heermann D, Roelofs L, et al. (1993) Monte Carlo simulation in statistical physics. Comput Phys 7: 156–157.    
  • 39. Andreo P (1991) Monte Carlo techniques in medical radiation physics. Phys Med Biol 36: 861.    
  • 40. Metropolis N, Ulam S (1949) The Monte Carlo method. J Am Stat Assoc 44: 335–341.    
  • 41. Chow JCL (2017) Internet-based computer technology on radiotherapy. Rep Pract Oncol Radiother 22: 455–462.    
  • 42. Chow JCL (2011) A performance evaluation on Monte Carlo simulation for radiation dosimetry using cell processor. J Comp Meth Sci Eng 11: 1–12.
  • 43. Chow JCL (2016) Performance optimization in 4D radiation treatment planning using Monte Carlo simulation on the cloud. J Comp Meth Sci Eng 16: 147–156.
  • 44. Wang H, Ma Y, Pratx G, et al. (2011) Toward real-time Monte Carlo simulation using a commercial cloud computing infrastructure. Phys Med Biol 56: N175.    
  • 45. Bernal MA, Bordage MC, Brown JM, et al. (2015) Track structure modeling in liquid water: A review of the Geant4-DNA very low energy extension of the Geant4 Monte Carlo simulation toolkit. Phys Med 31: 861–874.    
  • 46. Incerti S, Ivanchenko A, Karamitros M, et al. (2010) Comparison of GEANT4 very low energy cross section models with experimental data in water. Med Phys 37: 4692–4708.    
  • 47. Villagrasa C, Francis Z, Incerti S (2010) Physical models implemented in the GEANT4-DNA extension of the GEANT-4 toolkit for calculating initial radiation damage at the molecular level. Rad Prot Dosim 143: 214–218.
  • 48. Champion C, Incerti S, Perrot Y, et al. (2014) Dose point kernels in liquid water: An intra-comparison between GEANT4-DNA and a variety of Monte Carlo codes. Appl Radiat Isot 83: 137–141.    
  • 49. Butterworth KT, McMahon SJ, Currell FJ, et al. (2012) Physical basis and biological mechanisms of gold nanoparticle radiosensitization. Nanoscale 4: 4830–4838.    
  • 50. Montenegro M, Nahar SN, Pradhan AK, et al. (2009) Monte Carlo simulations and atomic calculations for Auger processes in biomedical nanotheranostics. J Phys Chem A 113: 12364–12369.
  • 51. He X, Cheng F, Chen ZX (2016) The lattice kinetic Monte Carlo simulation of atomic diffusion and structural transition for gold. Sci Rep 6: 33128.    
  • 52. Rogers DW, Walters B, Kawrakow I (2009) BEAMnrc users manual. Nrc Rep Pirs 509: 12.
  • 53. Martinov MP, Thomson RM (2017) Heterogeneous multiscale Monte Carlo simulations for gold nanoparticle radiosensitization. Med Phys 44: 644–653.    
  • 54. Sakata D, Kyriakou I, Okada S, et al. (2018) Geant4-DNA track-structure simulations for gold nanoparticles: The importance of electron discrete models in nanometer volumes. Med Phys 45: 2230–2242.    
  • 55. Brown JM, Dimmock MR, Gillam JE, et al. (2014) A low energy bound atomic electron Compton scattering model for Geant4. Nucl Instrum Meth B 338: 77–88.    
  • 56. Chow JCL, He C (2016) Gold nanoparticle DNA damage in radiotherapy: A Monte Carlo study. AIMS Bioeng 3: 352–361.    
  • 57. Cho SH (2005) Estimation of tumour dose enhancement due to gold nanoparticles during typical radiation treatments: A preliminary Monte Carlo study. Phys Med Biol 50: N163–N173.    
  • 58. Zhang SX, Gao J, Buchholz TA, et al. (2009) Quantifying tumor-selective radiation dose enhancements using gold nanoparticles: A Monte Carlo simulation study. Biomed Microdevices 11: 925–933.    
  • 59. Leung MK, Chow JCL, Chithrani BD, et al. (2011) Irradiation of gold nanoparticles by X-rays: Monte Carlo simulation of dose enhancements and the spatial properties of the secondary electrons production. Med Phys 38: 624–631.    
  • 60. Hwang C, Kim JM, Kim JH (2017) Influence of concentration, nanoparticle size, beam energy, and material on dose enhancement in radiation therapy. J Radiat Res 58: 405–411.    
  • 61. Douglass M, Bezak E, Penfold S (2013) Monte Carlo investigation of the increased radiation deposition due to gold nanoparticles using kilovoltage and megavoltage photons in a 3D randomized cell model. Med Phys 40: 071710.    
  • 62. Zygmanski P, Liu B, Tsiamas P, et al. (2013) Dependence of Monte Carlo microdosimetric computations on the simulation geometry of gold nanoparticles. Phys Med Biol 58: 7961–7977.    
  • 63. Cai Z, Pignol JP, Chattopadhyay N, et al. (2013) Investigation of the effects of cell model and subcellular location of gold nanoparticles on nuclear dose enhancement factors using Monte Carlo simulation. Med Phys 40: 114101.    
  • 64. Xie WZ, Friedland W, Li WB, et al. (2015) Simulation on the molecular radiosensitization effect of gold nanoparticles in cells irradiated by X-rays. Phys Med Biol 60: 6195–6212.    
  • 65. Lin AW, Lewinski NA, West JL, et al. (2005) Optically tunable nanoparticle contrast agents for early cancer detection: Model-based analysis of gold nanoshells. J Biomed Opt 10: 064035.    
  • 66. Zagaynova EV, Shirmanova MV, Kirillin MY, et al. (2008) Contrasting properties of gold nanoparticles for optical coherence tomography: Phantom, in vivo studies and Monte Carlo simulation. Phys Med Biol 53: 4995–5009.    
  • 67. Kirillin M, Shirmanova M, Sirotkina M, et al. (2009) Contrasting properties of gold nanoshells and titanium dioxide nanoparticles for optical coherence tomography imaging of skin: Monte Carlo simulations and in vivo study. J Biomed Opt 14: 021017.    
  • 68. Arifler D (2013) Nanoplatform-based optical contrast enhancement in epithelial tissues: Quantitative analysis via Monte Carlo simulations and implications on precancer diagnostics. Opt Express 21: 3693–3707.    
  • 69. Manohar N, Jones BL, Cho SH (2014) Improving X-ray fluorescence signal for benchtop polychromatic cone-beam X-ray fluorescence computed tomography by incident X-ray spectrum optimization: A Monte Carlo study. Med Phys 41: 101906.    
  • 70. Albayedh F, Chow JCL (2018) Monte Carlo simulation on the imaging contrast enhancement in nanoparticle-enhanced radiotherapy. J Med Phys 43: 195–199.    
  • 71. Lechtman E, Mashouf S, Chattopadhyay N, et al. (2013) A Monte Carlo-based model of gold nanoparticle radiosensitization accounting for increased radiobiological effectiveness. Phys Med Biol 58: 3075.    
  • 72. Amato E, Italiano A, Leotta S, et al. (2013) Monte Carlo study of the dose enhancement effect of gold nanoparticles during X-ray therapies and evaluation of the anti-angiogenic effect on tumour capillary vessels. J Xray Sci Technol 21: 237–247.
  • 73. Lin Y, Paganetti H, McMahon SJ (2015) Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons. Med Phys 42: 5890–5902.    
  • 74. Kakade NR, Sharma SD (2015) Dose enhancement in gold nanoparticle-aided radiotherapy for the therapeutic photon beams using Monte Carlo technique. J Cancer Res Ther 11: 94–97.    
  • 75. Zabihzadeh M, Moshirian T, Ghorbani M, et al. (2018) A Monte Carlo Study on Dose Enhancement by Homogeneous and Inhomogeneous Distributions of Gold Nanoparticles in Radiotherapy with Low Energy X-rays. J Biomed Phys Eng 8: 13–28.
  • 76. Brivio D, Zygmanski P, Arnoldussen M, et al. (2015) Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): A Monte Carlo evaluation. Phys Med Biol 60: 9203–9213.    
  • 77. Zheng XJ, Chow JCL (2017) Radiation dose enhancement in skin therapy with nanoparticle addition: A Monte Carlo study on kilovoltage photon and megavoltage electron beams. World J Radiol 2017 9: 63–71.
  • 78. Chow JCL, Leung MK, Jaffray DA (2012) Monte Carlo simulation on a gold nanoparticle irradiated by electron beams. Phys Med Biol 57: 3323–3331.    
  • 79. Mehrnia SS, Hashemi B, Mowla SJ, et al. (2017) Enhancing the effect of 4MeV electron beam using gold nanoparticles in breast cancer cells. Phys Med 35: 18–24.    
  • 80. Lin Y, Mcmahon SJ, Scarpelli M, et al. (2014) Comparing gold nano-particle enhanced radiotherapy with protons, megavoltage photons and kilovoltage photons: A Monte Carlo simulation. Phys Med Biol 59: 7675–7689.    
  • 81. Martínez-Rovira I, Prezado Y (2015) Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles. Med Phys 42: 6703–6710.    
  • 82. Cho J, Gonzalez-Lepera C, Manohar N, et al. (2016) Quantitative investigation of physical factors contributing to gold nanoparticle-mediated proton dose enhancement. Phys Med Biol 61: 2562–2581.    
  • 83. Bahreyni Toossi MT, Ghorbani M, Mehrpouyan M, et al. (2012) A Monte Carlo study on tissue dose enhancement in brachytherapy: A comparison between gadolinium and gold nanoparticles. Australas Phys Eng Sci Med 35: 177–185.    
  • 84. Asadi S, Vaez-zadeh M, Masoudi SF, et al. (2015) Gold nanoparticle-based brachytherapy enhancement in choroidal melanoma using a full Monte Carlo model of the human eye. J Appl Clin Med Phys 16: 344–357.    
  • 85. Asadi S, Vaez-Zadeh M, Vahidian M, et al. (2016) Ocular brachytherapy dosimetry for 103Pd and 125I in the presence of gold nanoparticles: A Monte Carlo study. J Appl Clin Med Phys 17: 90–99.
  • 86. Yan H, Ma X, Sun W, et al. (2018) Monte Carlo dosimetry modeling of focused kV X-ray radiotherapy of eye diseases with potential nanoparticle dose enhancement. Med Phys.
  • 87. Al-Musywel HA, Laref A (2017) Effect of gold nanoparticles on radiation doses in tumor treatment: A Monte Carlo study. Laser Med Sci 32: 2073–2080.    
  • 88. Lai P, Cai Z, Pignol JP (2017) Monte Carlo simulation of radiation transport and dose deposition from locally released gold nanoparticles labeled with 111In, 177Lu or 90Y incorporated into tissue implantable depots. Phys Med Biol 62: 8581–8599.    
  • 89. Dimitriou NM, Tsekenis G, Balanikas EC, et al. (2017) Gold nanopartirlces, radiations and the immune system: Current insights into the physical mechanisms and the biological interactions of this new alliance towards cancer therapy. Pharmacol Therapeut 78: 1–17.
  • 90. Mavragani IV, Nikitaki Z, Souli MP, et al. (2017) Complex DNA damage: A route to radiation-induced genomic instability and carcinogenesis. Cancers 9: 91.    


This article has been cited by

  • 1. Zakia Kanwal, Muhammad Raza, Farkhanda Manzoor, Saira Riaz, Ghazala Jabeen, Shafaq Fatima, Shahzad Naseem, A Comparative Assessment of Nanotoxicity Induced by Metal (Silver, Nickel) and Metal Oxide (Cobalt, Chromium) Nanoparticles in Labeo rohita, Nanomaterials, 2019, 9, 2, 309, 10.3390/nano9020309
  • 2. F Hespeels, A C Heuskin, T Tabarrant, E Scifoni, M Kraemer, G Chêne, D Strivay, S Lucas, Backscattered electron emission after proton impact on gold nanoparticles with and without polymer shell coating, Physics in Medicine & Biology, 2019, 64, 12, 125007, 10.1088/1361-6560/ab195f
  • 3. Aniza Abdulle, James C. L. Chow, Contrast Enhancement for Portal Imaging in Nanoparticle-Enhanced Radiotherapy: A Monte Carlo Phantom Evaluation Using Flattening-Filter-Free Photon Beams, Nanomaterials, 2019, 9, 7, 920, 10.3390/nano9070920
  • 4. James Chun Lam Chow, , Handbook of Nanomaterials and Nanocomposites for Energy and Environmental Applications, 2020, Chapter 2-1, 1, 10.1007/978-3-030-11155-7_2-1
  • 5. Dewmini Mututantri-Bastiyange, James C. L. Chow, Imaging dose of cone-beam computed tomography in nanoparticle-enhanced image-guided radiotherapy: A Monte Carlo phantom study, AIMS Bioengineering, 2020, 7, 1, 1, 10.3934/bioeng.2020001
  • 6. Stefano Martelli, James C L Chow, Dose Enhancement for the Flattening-Filter-Free and Flattening-Filter Photon Beams in Nanoparticle-Enhanced Radiotherapy: A Monte Carlo Phantom Study, Nanomaterials, 2020, 10, 4, 637, 10.3390/nano10040637
  • 7. Megha Sharma, James C. L. Chow, Skin dose enhancement from the application of skin-care creams using FF and FFF photon beams in radiotherapy: A Monte Carlo phantom evaluation, AIMS Bioengineering, 2020, 7, 2, 82, 10.3934/bioeng.2020008
  • 8. Adam Konefał, Wioletta Lniak, Justyna Rostocka, Andrzej Orlef, Maria Sokół, Janusz Kasperczyk, Paulina Jarząbek, Aleksandra Wrońska, Katarzyna Rusiecka, Influence of a shape of gold nanoparticles on the dose enhancement in the wide range of gold mass concentration for high-energy X-ray beams from a medical linac, Reports of Practical Oncology & Radiotherapy, 2020, 25, 4, 579, 10.1016/j.rpor.2020.05.003

Reader Comments

your name: *   your email: *  

© 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved