Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Radiosensitization effects of BaTiO₃ and gold nanoparticles in proton therapy of pancreatic tumors: A Monte Carlo study

Articles in Press

Document Type : Original Article

Authors
Elham Mansouri 1
Parinaz Mehnati 1, 2
1 Medical Radiation Sciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Medical Physics Department, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
10.22038/ijbms.2026.95085.20513
Abstract
Objective(s): This study investigates the potential of barium titanate (BaTiO3) nanoparticles to enhance the therapeutic efficacy of proton therapy for pancreatic tumors in comparison to gold nanoparticles through both macroscopic and microscopic simulations.
Materials and Methods: Using the MCNP6.1 Monte Carlo code, we modeled a 3cm pancreatic tumor in the head of the pancreas loaded with clusters of BaTiO3 and gold nanoparticles using a lattice model. Proton beam (SOBP, 135 MeV) interactions were simulated to evaluate the dose enhancement factor (DEF) within the tumor, the non-tumor pancreas, and Organs At Risks (OARs). Additionally, microscopic dosimetry was conducted to study the dose deposition in the vicinity of the clusters containing nanoparticles.
Results: The gold nanoparticles present DEF of 1.21 and BaTiO3 nanoparticles present DEF of 1.14 in the tumor site. The OARs remained mainly unaffected. Also, on a microscopic scale, DEF values of 1.7-1.83 in the presence of gold nanoparticles and 1.42-1.51 in the presence of BaTiO3 nanoparticles were calculated. The microscopic DEFs were more than the macroscopic DEF.
Conclusion: Both gold and BaTiO₃ nanoparticles enhanced proton dose deposition, with gold nanoparticles producing greater macroscopic and microscopic DEFs. The results also show that microscopic dose enhancement exceeds macroscopic dose enhancement, confirming that most proton-induced dose enhancement occurs in the close vicinity of nanoparticles. Because this study is based on Monte Carlo simulations with a uniform nanoparticle distribution and without biological modeling, further experimental studies are needed to validate these findings.
Keywords
Barium titanate
MCNP6
Pancreatic tumor
Proton therapy
Radiosensitization
Subjects
1. Bazeed AY, Day CA-O, Garg SA-O. Pancreatic cancer: Challenges and opportunities in locoregional therapies. Cancers (Basel) 2022;14:4257.
2. Kobeissi JA-O, Simone CBnA-O, Lin H, Hilal LA-O, Hajj C. Proton therapy in the management of pancreatic cancer. Cancers (Basel) 2022;14:2789. 
3. Ma J, Shen H, Mi ZA-O. Enhancing proton therapy efficacy through nanoparticle-mediated radiosensitization. Cells 13:1841.
4. Mansouri E, Almisned G, Tekin HO, Rajabpour S, Mesbahi A. Radiosensitization with metallic nanoparticles under MeV proton beams: local dose enhancement. Radiat Environ Biophys 2024; 63:537-543.
5. Liu Y, Li B, Wang L. Potential applications of metal-based nanomaterials in tumor radiotherapy: from x-ray to particle therapies. Cancer Nanotechnol 2025; 16:42.
6. Ma J, Shen H, Mi Z. Enhancing proton therapy efficacy through nanoparticle-mediated radiosensitization. Cells 2024; 13:1841.
7. Montazersaheb S, Farahzadi R, Mansouri E, Jafari S, Fathi E. Radiosensitizing effects of silver nanoparticles targeting angiogenesis and matrix metalloproteinase signaling in triple negative breast cancer cell lines. Sci Rep 2026;16:6820.
8. Raj D, M.V M, K S, Mohan CC, Bhat SG. Anticancer potential of Barium titanate nanoparticles: Structural, optical and biomedical perspectives. Results Surf. Interfaces 2025; 20:100584.
9.Mansouri E, Mesbahi A, Hejazi MS, Tarhriz V, Hamishehkar H, Seyednejad F. A comprehensive analysis of radiosensitization properties of metallic nanoparticles in brachytherapy of gastric adenocarcinoma by I-125 seed: A simulation study by MCNPX and MCNP6 codes. Magnetochemistry 2022; 8:1-10.
10. Çağlar MA-O, Eşitmez DA-O, Cebe MA-O. The Effect of Dose Enhancement in Tumor With Silver Nanoparticles on Surrounding Healthy Tissues: A Monte Carlo Study. Technol Cancer Res Treat 2024; 23:15330338241235771.
11. Zhang X, Xie X, Qu D, Ning J, Zhou H, Pan J, et al. Determining organ dose conversion coefficients for external neutron irradiation by using a voxel mouse model. J Radiat Res 2016;57:182-188.
12. Hadiyan fard M, Baghani HR, Shamsabadi R, Aminafshar B. Effect of nanoparticle distribution scenario on tissue dose corrections: A Monte Carlo simulation study. Radiat Phys Chem 2026; 244:113806.
13. Martinov MP, Fletcher EM, Thomson RM. Multiscale monte Carlo simulations of gold nanoparticle dose-enhanced radiotherapy I: Cellular dose enhancement in microscopic models. Med Phys 2023;50:5842-5852.
14. Sung W, Ye SJ, McNamara AL, McMahon SJ, Hainfeld J, Shin  J et al. Dependence of gold nanoparticle radiosensitization on cell geometry. Nanoscale 2017;9:5843-5853.
15. Lin Y, McMahon SJ, Scarpelli M, Paganetti H, Schuemann J. Comparing gold nano-particle enhanced radiotherapy with protons, megavoltage photons and kilovoltage photons: A Monte Carlo simulation. Comparative Study Phys Med Biol 2014;59:7675-7689.
16. Misawa M, Takahashi J. Generation of reactive oxygen species induced by gold nanoparticles under x-ray and UV Irradiations. Nanomed Nanotechnol Biol Med 2011; 7: 604-614.
17. McMahon SJ, Hyland WB, Muir MF, Coulter JA, Jain S, Butterworth KT, et al. Biological consequences of nanoscale energy deposition near irradiated heavy atom nanoparticles. Sci Rep 2011; 1:18.
18. Hainfeld JF, Smilowitz HM, O’Connor MJ, Dilmanian FA, Slatkin DN. Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine 2013;8:1601-1609.
19. Cho J, Gonzalez-Lepera C, Manohar N, Kerr M, Krishnan S, Cho SH. Quantitative investigation of physical factors contributing to gold nanoparticle-mediated proton dose enhancement. Phys Med Biol 2016; 61:2562-2581.
20. Cunningham C, de Kock M, Engelbrecht M, Miles X, Slabbert J, Vandevoorde C. Radiosensitization effect of gold nanoparticles in proton therapy. Front Public Health 2021; 9:699822.
21. Tabbakh F. Significance of the proton energy loss mechanism to gold nanoparticles in proton therapy: A Geant4 simulation. Sci Rep 2024; 14:24978.
22. Ahmadi Ganjeh Z, Salehi Z. Monte Carlo study of nanoparticles effectiveness on the dose enhancement when irradiated by protons. AIP Advances 2023; 13: 0350181-0350186.
23. 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; 32:1584-1593.
24. Engels E, Corde S, McKinnon S, Incerti S, Konstantinov K, Rosenfeld A, et al. Optimizing dose enhancement with Ta2O5 nanoparticles for synchrotron microbeam activated radiation therapy. Physica Medica 2016; 32:1852-1861.
25. Kwon J, Sutherland K, Hashimoto T, Date H. Dose Distribution of electrons from gold nanoparticles by proton beam irradiation. Int J Med Phys Clin Eng Radiat Oncol 2015; 04:49-53.
26. Lin Y, McMahon Sj, Paganetti H, Paganetti H, Schuemann J, Schuemann J. Biological modeling of gold nanoparticle enhanced radiotherapy for proton therapy. Phys Med Biol 2015;60:4149-4168.
27. Abdul Rashid R, Zainal Abidin S, Khairil Anuar MA, 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.
28. Wälzlein C, Scifoni E, Krämer M, Durante M. Simulations of dose enhancement for heavy atom nanoparticles irradiated by protons. Phys Med Biol 2014; 59:1441.
29. Rahmawati F, Khairunnisa AF, Riyatun, Suharyana. Analysis of dose distribution in proton therapy for lung cancer with MCNP code. J Phys Conf 2022; 2190:012021.
30. Filimonova MV, Soldatova OV, Shitova AA, Filimonov AS, Rybachuk VA, Kosachenko AO, et al. Bismuth nanoparticles increase effectiveness of proton therapy of ehrlich carcinoma. Bull Exp Biol Med 2024; 176:626-630.
31. 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. Phys Med Biol 2010; 55:931.
32. Kim JK, Seo SJ, Kim KH, Kim TJ, Chung MH, Kim KR, Yang TK, et al. Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect. Nanotechnology 2010; 21:425102.
33. Polf JC, Bronk LF, Driessen WHP, Arap W, Pasqualini R, Gillin M. Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles. Appl Phys Lett 2011; 98:193702.
34. Zavestovskaya IN, Filimonova MV, Popov AL, Zelepukin IV, Shemyakov AE, Tikhonowski GV, et al. Bismuth nanoparticles-enhanced proton therapy: Concept and biological assessment. Materials Today Nano 2024; 27:100508.
35. Baluchamy S, Ravichandran P, Periyakaruppan A, Ramesh V, Hall JC, Zhang Y, et al. Induction of cell death through alteration of oxidants and antioxidants in lung epithelial cells exposed to high energy protons. J Biol Chem 2010; 285:24769-24774.
36. Tucci P, Porta G, Agostini M, Dinsdale D, Iavicoli I, Cain K, et al. Metabolic effects of TiO2 nanoparticles, a common component of sunscreens and cosmetics, on human keratinocytes. Cell Death Dis 2013; 4:e549-e549.
37. Gerken LRH, Gogos A, Starsich FHL, David H, Gerdes ME, Schiefer H, et al. Catalytic activity imperative for nanoparticle dose enhancement in photon and proton therapy. Nat Commun 2022; 13:3248.
38. Sadeghi M, Ansari Z, Kakavand T. Targetry for 48 V production and the nuclear model calculation on the charge particle induced reaction on Ti target. J Radioanal Nucl Chem 2012; 293:7-12.
39. Ahamed M, Akhtar MJ, Khan MAM, Alhadlaq HA, Alshamsan A. Barium titanate (batio3) nanoparticles exert cytotoxicity through oxidative stress in human lung carcinoma (a549) cells. Nanomaterials 2020; 10:2309.
Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 26 August 2026