Investigation of the effect of nanoparticle physical parameters on the efficiency of proton therapy for brain tumors using Monte Carlo simulation

Bidokhti, Parisa; Karimi Shahri, Keyhandokht; Ghorbani, Mehdi

Volume 14, Issue 1 (3-2026) jmsthums 2026, 14(1): 61-75 | Back to browse issues page

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Bidokhti P, Karimi Shahri K, Ghorbani M. Investigation of the effect of nanoparticle physical parameters on the efficiency of proton therapy for brain tumors using Monte Carlo simulation. jmsthums 2026; 14 (1) :61-75
URL: http://jms.thums.ac.ir/article-1-1470-en.html

Investigation of the effect of nanoparticle physical parameters on the efficiency of proton therapy for brain tumors using Monte Carlo simulation

Parisa Bidokhti¹

, Keyhandokht Karimi Shahri¹

, Mehdi Ghorbani²

1- Department of Physics, Faculty of Science, University of Birjand, Birjand, Iran
2- Biomedical Engineering and Medical Physics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract: (13 Views)

Background & Aim: Proton therapy is a highly effective method for treating complex cancers due to its precise dose distribution. However, enhancing its efficacy remains challenging. One promising approach is the use of nanoparticles as radiosensitizers. This study evaluates the effect of different nanoparticles on dose enhancement in proton therapy, using Monte Carlo simulation.
Methods: A water phantom with dimensions of 13.2 × 17.2 × 13.2 cm³ was placed at the center of a 100cm-radius world cell and contained a 2-cm cubic tumor and a 120 MeV proton beam was simulated using the MCNP6.1. Monte Carlo code. Gold, hafnium oxide, and iron oxide nanoparticles were homogeneously distributed within the tumor using repeated geometry. Fourteen simulations, each with 10⁹ particles, were run to achieve <1% statistical error. The dose enhancement factor was then calculated, and the impact of nanoparticle size and concentration were investigated.
Results: Gold nanoparticles at a concentration of 30 mg/mL and a size of 50 nm yielded the highest DEF (2.2%), while hafnium oxide and iron oxide nanoparticles showed lower enhancement. Increasing the concentration of nanoparticles resulted in a more than four-fold increase in the dose enhancement factor (from 0.5% to 2.2%), whereas increasing the size of nanoparticle reduced the dose enhancement factor from 2.2% to 1.71%. This suggests that concentration has a greater impact on the dose enhancement factor than size.
Conclusion: Gold nanoparticles produced the highest dose enhancement due to their high density. Additionally, the concentration of nanoparticle has a greater impact on dose enhancement than their size. Therefore, selection of nanoparticle type and characteristics is crucial for improving proton therapy. Further studies are needed to understand biological effects of these nanoparticles.

Keywords: Proton Therapy, Nanoparticles, Monte Carlo Method, Radiation Dosage

Full-Text [PDF 506 kb] (35 Downloads)

Type of Study: Research | Subject: Special
Received: 2025/08/10 | Accepted: 2025/12/17 | Published: 2026/06/29

References

1. Suit H, DeLaney T, Goldberg S, Paganetti H, Clasie B, Gerweck L, et al. Proton vs carbon ion beams in the definitive radiation treatment of cancer patients. Radiotherapy and Oncology. 2010;95(1):3-22. [DOI:10.1016/j.radonc.2010.01.015]

2. Howard ME, Beltran C, Anderson S, Tseung WC, Sarkaria JN, Herman MG. Investigating dependencies of relative biological effectiveness for proton therapy in cancer cells. International journal of particle therapy. 2017;4(3):12-22. [DOI:10.14338/IJPT-17-00031.1]

3. Vasudevan SS, Candelo E, Sharifi A, Ma DJ, Patel SH, Routman DM, et al. Survival, Tumor Control, and Safety Outcomes of Proton Therapy in Sinonasal Cancer Population: A Systematic Review and Meta‐Analysis. Head & Neck. 2025;47(4):1291-305. [DOI:10.1002/hed.28082]

4. Frank SJ, Cox JD, Gillin M, Mohan R, Garden AS, Rosenthal DI, et al. Multifield optimization intensity modulated proton therapy for head and neck tumors: a translation to practice. International Journal of Radiation Oncology* Biology* Physics. 2014;89(4):846-53. [DOI:10.1016/j.ijrobp.2014.04.019]

5. Hutcheson K, Lewin J, Garden A, Rosenthal D, Weber R, William W, et al. Early experience with IMPT for the treatment of oropharyngeal tumors: Acute toxicities and swallowing-related outcomes. International Journal of Radiation Oncology, Biology, Physics. 2013;87(2):S604. [DOI:10.1016/j.ijrobp.2013.06.1597]

6. Carbone GG, Mariano S, Gabriele A, Cennamo S, Primiceri V, Aziz MR, et al. Exploring the potential of gold nanoparticles in proton therapy: Mechanisms, advances, and clinical horizons. Pharmaceutics. 2025;17(2):176. [DOI:10.3390/pharmaceutics17020176]

7. Ma J, Shen H, Mi Z. Enhancing proton therapy efficacy through nanoparticle-mediated radiosensitization. Cells. 2024;13(22):1841. [DOI:10.3390/cells13221841]

8. Hosobuchi M, Kataoka J, Yokokawa H, Okazaki Y, Hirayama R, Inaniwa T, et al. Experimental verification of efficacy of pBCT in terms of physical and biological aspects. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 2023;1045:167537. [DOI:10.1016/j.nima.2022.167537]

9. Ahmadi Ganjeh Z, Salehi Z. Monte Carlo study of nanoparticles effectiveness on the dose enhancement when irradiated by protons. AIP Advances. 2023;13(3). [DOI:10.1063/5.0135572]

10. Huynh NH, Chow JC. DNA dosimetry with gold nanoparticle irradiated by proton beams: A Monte Carlo study on dose enhancement. Applied Sciences. 2021;11(22):10856. [DOI:10.3390/app112210856]

11. Velten C, Tomé WA. Reproducibility study of Monte Carlo simulations for nanoparticle dose enhancement and biological modeling of cell survival curves. Biomedical Physics & Engineering Express. 2023;9(4):045004. [DOI:10.1088/2057-1976/acd1f1]

12. Ahn SH. Monte Carlo investigation of dose enhancement due to gold nanoparticle in carbon-12, helium-4, and proton beam therapy. Progress in Medical Physics. 2022;33(4):114-20. [DOI:10.14316/pmp.2022.33.4.114]

13. Powers S. Ranges for protons and alpha particles. icru report 49. Bethesda, MD. 1993.

14. Liu C-J, Wang C-H, Chen S-T, Chen H-H, Leng W-H, Chien C-C, et al. Enhancement of cell radiation sensitivity by pegylated gold nanoparticles. Physics in Medicine & Biology. 2010;55(4):931. [DOI:10.1088/0031-9155/55/4/002]

15. Cunningham C, de Kock M, Engelbrecht M, Miles X, Slabbert J, Vandevoorde C. Radiosensitization effect of gold nanoparticles in proton therapy. Frontiers in Public Health. 2021;9:699822. [DOI:10.3389/fpubh.2021.699822]

16. Zwiehoff S, Johny J, Behrends C, Landmann A, Mentzel F, Bäumer C, et al. Enhancement of proton therapy efficiency by noble metal nanoparticles is driven by the number and chemical activity of surface atoms. Small. 2022;18(9):2106383. [DOI:10.1002/smll.202106383]

17. Schlathölter T, Eustache P, Porcel E, Salado D, Stefancikova L, Tillement O, et al. Improving proton therapy by metal-containing nanoparticles: Nanoscale insights. International journal of nanomedicine. 2016:1549-56. [DOI:10.2147/IJN.S99410]

18. Rashid RA, Abidin SZ, Anuar MAK, Tominaga T, Akasaka H, Sasaki R, et al. Radiosensitization effects and ROS generation by high Z metallic nanoparticles on human colon carcinoma cell (HCT116) irradiated under 150 MeV proton beam. OpenNano. 2019;4:100027. [DOI:10.1016/j.onano.2018.100027]

19. Gerken LR, Gogos A, Starsich FH, David H, Gerdes ME, Schiefer H, et al. Catalytic activity imperative for nanoparticle dose enhancement in photon and proton therapy. Nature communications. 2022;13(1):3248. [DOI:10.1038/s41467-022-30982-5]

20. Brero F, Calzolari P, Albino M, Antoccia A, Arosio P, Berardinelli F, et al. Proton therapy, magnetic nanoparticles and hyperthermia as combined treatment for pancreatic BxPC3 tumor cells. Nanomaterials. 2023;13(5):791. [DOI:10.3390/nano13050791]

21. Tabbakh F. Significance of the proton energy loss mechanism to gold nanoparticles in proton therapy: a Geant4 simulation. Scientific Reports. 2024;14(1):24978. [DOI:10.1038/s41598-024-76244-w]

22. Cao Y, Zhou X, Nie Q, Zhang J. Inhibition of the thioredoxin system for radiosensitization therapy of cancer. European Journal of Medicinal Chemistry. 2024;268:116218. [DOI:10.1016/j.ejmech.2024.116218]

23. Shrestha S, Cooper LN, Andreev OA, Reshetnyak YK, Antosh MP. Gold nanoparticles for radiation enhancement in vivo. Jacobs journal of radiation oncology. 2016;3(1):026.

24. Tsiamas P, Liu B, Cifter F, Ngwa WF, Berbeco RI, Kappas C, et al. Impact of beam quality on megavoltage radiotherapy treatment techniques utilizing gold nanoparticles for dose enhancement. Physics in Medicine & Biology. 2013;58(3):451. [DOI:10.1088/0031-9155/58/3/451]

25. Akhdar H, Alanazi R, Alanazi N, Alodhayb A. Secondary electrons in gold nanoparticle clusters and their role in therapeutic ratio: the outcome of a Monte Carlo simulation study. Molecules. 2022;27(16):5290. [DOI:10.3390/molecules27165290]

26. Mohseni M, Kazemzadeh A, Ataei N, Moradi H, Aliasgharzadeh A, Farhood B. Study on the dose enhancement of gold nanoparticles when exposed to clinical electron, proton, and alpha particle beams by means of Geant4. Journal of Medical Signals & Sensors. 2020;10(4):286-94. [DOI:10.4103/jmss.JMSS_58_19]

27. Ghita M, McMahon SJ, Taggart LE, Butterworth KT, Schettino G, Prise KM. A mechanistic study of gold nanoparticle radiosensitisation using targeted microbeam irradiation. Scientific reports. 2017;7(1):44752. [DOI:10.1038/srep44752]

28. Yusuf A, Almotairy ARZ, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as drug delivery systems: a review of the implication of nanoparticles' physicochemical properties on responses in biological systems. Polymers. 2023;15(7):1596. [DOI:10.3390/polym15071596]

29. Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to enhance radiotherapy in mice. Physics in Medicine & Biology. 2004;49(18):N309. [DOI:10.1088/0031-9155/49/18/N03]

30. Chithrani BD, Ghazani AA, Chan WC. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano letters. 2006;6(4):662-8. [DOI:10.1021/nl052396o]

31. Ghorbani M, Jia SB, Khosroabadi M, Sadoughi HR, Knaup C. Evaluation of the effect of soft tissue composition on the characteristics of spread-out Bragg peak in proton therapy. Journal of Cancer Research and Therapeutics. 2017;13(6):974-80. [DOI:10.4103/0973-1482.220420]

32. Malmir S, Molavi AA, Mohammadi S. The evaluation of dose enhancement within gold nanoparticle radio-sensitized tumor using proton therapy. Journal of Isfahan Medical School. 2016;34(408):1414-22.

33. Carron NJ. An introduction to the passage of energetic particles through matter: Taylor & Francis; 2006. [DOI:10.1201/9781420012378]

34. Friedland W, Schmitt E, Kundrát P, Dingfelder M, Baiocco G, Barbieri S, et al. Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping. Scientific reports. 2017;7(1):45161. [DOI:10.1038/srep45161]

35. Barendsen G. The relationships between RBE and LET for different types of lethal damage in mammalian cells: biophysical and molecular mechanisms. Radiation research. 1994;139(3):257-70. [DOI:10.2307/3578823]

36. Martínez‐Rovira I, Prezado Y. Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles. Medical physics. 2015;42(11):6703-10. [DOI:10.1118/1.4934370]

37. Verkhovtsev AV, Korol AV, Solov'yov AV. Revealing the mechanism of the low-energy electron yield enhancement from sensitizing nanoparticles. Physical Review Letters. 2015;114(6):063401. [DOI:10.1103/PhysRevLett.114.063401]

38. Peukert D, Kempson I, Douglass M, Bezak E. 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. Medical Physics. 2020;47(2):651-61. [DOI:10.1002/mp.13923]

39. Rajabpour S, Saberi H, Rasouli J, Jabbari N. Comparing Geant4 physics models for proton-induced dose deposition and radiolysis enhancement from a gold nanoparticle. Scientific Reports. 2022;12(1):1779. [DOI:10.1038/s41598-022-05748-0]

40. Sotiropoulos M, Taylor M, Henthorn N, Warmenhoven J, Mackay R, Kirkby K, et al. Geant4 interaction model comparison for dose deposition from gold nanoparticles under proton irradiation. Biomedical Physics & Engineering Express. 2017;3(2):025025. [DOI:10.1088/2057-1976/aa69cc]

41. Belousov A, Morozov V, Krusanov G, Moiseev A, Davydov A, Shtil A, et al. The change in the linear energy transfer of a clinical proton beam in the presence of gold nanoparticles. Biophysics. 2020;65(4):541-7. [DOI:10.1134/S0006350920040053]

42. McKinnon S, Guatelli S, Incerti S, Ivanchenko V, Konstantinov K, Corde S, et al. Local dose enhancement of proton therapy by ceramic oxide nanoparticles investigated with Geant4 simulations. Physica Medica. 2016;32(12):1584-93. [DOI:10.1016/j.ejmp.2016.11.112]

43. Polf JC, Bronk LF, Driessen WH, Arap W, Pasqualini R, Gillin M. Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles. Applied physics letters. 2011;98(19). [DOI:10.1063/1.3589914]

44. Penninckx S, Heuskin A-C, Michiels C, Lucas S. Gold nanoparticles as a potent radiosensitizer: A transdisciplinary approach from physics to patient. Cancers. 2020;12(8):2021. [DOI:10.3390/cancers12082021]

45. Kyriakou I, Sakata D, Tran HN, Perrot Y, Shin W-G, Lampe N, et al. Review of the Geant4-DNA simulation toolkit for radiobiological applications at the cellular and DNA level. Cancers. 2021;14(1):35. [DOI:10.3390/cancers14010035]