Analysis of physical dose enhancement in nano-scale for nanoparticle-based radiation therapy: a Cluster and endothelial cell model

Document Type : Research Paper


1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Molecular Medicine Research center, Tabriz University of Medical Sciences, Tabriz, Iran

3 Medical Radiation Sciences Research Team, Tabriz University of Medical Sciences, Tabriz, Iran


Objective(s): One major difficulty of conventional radiotherapy is the lack of selectivity between the tumor and the organs at risk. In nanoparticle aided radiotherapy, heavy elements are present at higher concentrations in the tumor than normal tissues. This study aimed to model the characteristics of secondary electrons generated from the interaction of clusters comprised of five different nanoparticles including Gold, Gadolinium, Iridium, Bismuth, and Hafnium atoms with low energy x-rays (similar to brachytherapy sources in terms of energy) as a function of nanoparticle size and beam energy.
Materials and Methods: To better evaluate the contributions of secondary electrons in energy deposition, and also to develop a framework in analyzing further measurements in the future, we attempted to enhance and promote existing mathematical models for energy deposition in endothelial cells by nanoparticle-enhanced radiotherapy. Also, the MCNPX Monte Carlo code was used to model the identical geometry and the dose enhancement factor was calculated for all types of simulated nano-clusters.
Results: Our results showed that for our model consist of a nano-cluster and an endothelial cell the DEF significantly depends on the energy of photons and L- and K-edge binding energy of the atoms inside the nano-cluster. However, for Gd at the energy 60 keV, a higher dose enhancement factor was seen.
Conclusion: It can be concluded that the mathematical model considers the DEF variation with photon energy and the effect of NP type is considered in DEF calculations. However, the MC method has indicated very high sensitivity to photon energy, and NP type compared to the mathematical method.


1.Yazdani P, Mansouri E, Eyvazi S, Yousefi V, Kahroba H, Hejazi MS. Layered double hydroxide nanoparticles as an appealing nanoparticle in gene/plasmid and drug delivery system in C2C12 myoblast cells. Artif Cells Nanomed Biotechnol. . 2019; 47(1): 436-442.
2.Mansouri E, Tarhriz V, Yousefi V, Dilmaghani A. Intercalation and release of an anti-inflammatory drug into designed three-dimensionally layered double hydroxide nanostructure via calcination–reconstruction route. Adsorption. 2020.
3.Ghavami SM, Ghiasi H, Mesbahi A. Monte Carlo modeling of the yttrium-90 nanospheres application in the liver radionuclide therapy and organs doses calculation. Nucl Technol Radiat Prot. 2016; 31(1): 89-96.
4.Mesbahi A, Famouri F, Ahar MJ, Ghaffari MO, Ghavami SM. A study on the imaging characteristics of Gold nanoparticles as a contrast agent in X-ray computed tomography. PJMPE. 2017; 23(1): 9-14.
5.Pirayesh Islamian J, Hatamian M, Aval NA, Rashidi MR, Mesbahi A, Mohammadzadeh M. Targeted superparamagnetic nanoparticles coated with 2-deoxy-D-gloucose and doxorubicin more sensitize breast cancer cells to ionizing radiation. Breast. 2017;33: 97-103.
6.Mesbahi A, Ghiasi H. Shielding properties of the ordinary concrete loaded with micro- and nano-particles against neutron and gamma radiations. Appl Radiat Isot. 2018; 136: 27-31.
7.Verdipoor K, Alemi A, Mesbahi A. Photon mass attenuation coefficients of a silicon resin loaded with WO3, PbO, and Bi2O3 Micro and Nano-particles for radiation shielding. Radiat Phys Chem. 2018; 147: 85-90.
8.Badrigilan S, Shaabani B, Gharehaghaji N, Mesbahi A. Iron oxide/bismuth oxide nanocomposites coated by graphene quantum dots: “Three-in-one” theranostic agents for simultaneous CT/MR imaging-guided in vitro photothermal therapy. Photodiagnosis Photodyn Ther. 2019; 25: 504-514.
9.Jangjoo AG, Ghiasi H, Mesbahi A. A Monte Carlo study on the radio-sensitization effect of gold nanoparticles in brachytherapy of prostate by 103Pd seeds. PJMPE. 2019; 25(2): 87-92.
10.Khodadadi A, Nedaie HA, Sadeghi M, Ghassemi MR, Mesbahi A, Banaee N. Determination of the dose enhancement exclusively in tumor tissue due to the presence of GNPs. Appl Radiat Isot. 2019; 145: 39-46.
11.Malekzadeh R, Mehnati P, Sooteh MY, Mesbahi A. Influence of the size of nano- and microparticles and photon energy on mass attenuation coefficients of bismuth–silicon shields in diagnostic radiology. Radiol Phys Technol. 2019; 12(3): 325-334.
12.Mesbahi A, Verdipoor K, Zolfagharpour F, Alemi A. Investigation of fast neutron shielding properties of new polyurethane-based composites loaded with B4C, BeO, WO3, ZnO, and Gd2O3 micro-and nanoparticles. Pjmpe. 2019; 25(4): 211-219.
13.Zareei L, Divband B, Mesbahi A, Khatamian M, Kiani A, Gharehaghaji N. A new potential contrast agent for magnetic resonance imaging: Iron Oxide-4A nanocomposite. JBPE. 2019; 9(2): 211-216.
14.Afkham Y, Mesbahi A, Alemi A, Zolfagharpour F, Jabbari N. Design and fabrication of a Nano-based neutron shield for fast neutrons from medical linear accelerators in radiation therapy. Radiat Oncol. 2020; 15(1).
15.Badrigilan S, Shaabani B, Aghaji NG, Mesbahi A. Graphene Quantum Dots-Coated Bismuth Nanoparticles for Improved CT Imaging and Photothermal Performance. Int J Nanosci. 2020; 19(1).
16.Mortezazadeh T, Gholibegloo E, Khoobi M, Alam NR, Haghgoo S, Mesbahi A. In vitro and in vivo characteristics of doxorubicin-loaded cyclodextrine-based polyester modified gadolinium oxide nanoparticles: a versatile targeted theranostic system for tumour chemotherapy and molecular resonance imaging. J Drug Target. 2020; 28(5): 533-546.
17.Sadeghian M, Akhlaghi P, Mesbahi A. Investigation of imaging properties of novel contrast agents based on gold, silver and bismuth nanoparticles in spectral computed tomography using Monte Carlo simulation. PJMPE. 2020; 26(1): 21-29.
18.Verdipoor K, Mesbahi A. Radiation shielding features of ordinary and high-density concretes loaded with PbO micro and nanoparticles against high-energy photons. IJMP. 2020; 17(3): 205-212.
19.Butterworth K, Wyer JA, Fournet M, Latimer C, Shah M, Currell F. Variation of Strand Break Yield for Plasmid DNA Irradiated with High-Z Metal Nanoparticles. Radiat Res. 2008; 170: 381-387.
20.Bazak R, Houri M, El Achy S, Kamel S, Refaat T. Cancer active targeting by nanoparticles: a comprehensive review of literature. J Cancer Res Clin Oncol. 2015; 141(5): 769-784.
21.Zheng Y, Sanche L. Gold nanoparticles enhance DNA damage induced by anti-cancer drugs and radiation. Radiation research. 2009;172(1):114-9.
22.Cooper DR, Bekah D, Nadeau JL. Gold nanoparticles and their alternatives for radiation therapy enhancement. Front Chem. 2014; 2(86).
23.Jain S, Hirst DG, O’Sullivan JM. Gold nanoparticles as novel agents for cancer therapy. Br J Radiol. 2012; 85(1010): 101-113.
24.Vallières S. Dose Enhancement with Nanoparticles in Radiotherapy Using Gold-Doxorubicin Conjugates 2016.
25.Berbeco RI, Ngwa W, Makrigiorgos GM. Localized dose enhancement to tumor blood vessel endothelial cells via megavoltage X-rays and targeted gold nanoparticles: new potential for external beam radiotherapy. Int J Radiat Oncol. 2011; 81: 270.
26.Hainfeld JF, Dilmanian FA, Slatkin DN, Smilowitz HM. Radiotherapy enhancement with gold nanoparticles. J Pharm Pharmacol. 2008; 60: 977.
27.Hildenbrand G, Metzler P, Pilarczyk G, Bobu V, Kriz W, Hosser H. Dose enhancement effects of gold nanoparticles specifically targeting RNA in breast cancer cells. PLoS One. 2018; 13(1): e0190183-e.
28.Leung MK, Chow JC, Chithrani BD, Lee MJ, Oms B, Jaffray DA. Irradiation of gold nanoparticles by x-rays: Monte Carlo simulation of dose enhancements and the spatial properties of the secondary electrons production. Med Phys. 2011; 38(2): 624-631.
29.Mesbahi A, Jamali F, Gharehaghaji N. Effect of Photon Beam Energy, Gold Nanoparticle Size and Concentration on the Dose Enhancement in Radiation Therapy. BioImpacts : BI. 2013; 3: 29-35.
30.Kobayashi K, Usami N, Porcel E, Lacombe S, Le Sech C. Enhancement of radiation effect by heavy elements. Mutat Res. 2010; 704: 123.
31.Butterworth KT, McMahon SJ, Currell FJ, Prise KM. Physical basis and biological mechanisms of gold nanoparticle radiosensitization. Nanoscale. 2012; 4(16): 4830-4838.
32.Roeske JC, Nunez L, Hoggarth M, Labay E, Weichselbaum RR. Characterization of the theorectical radiation dose enhancement from nanoparticles. Technol Cancer Res Treat. 2007; 6(5): 395-401.
33.Zygmanski P, Sajo E. Nanoscale radiation transport and clinical beam modeling for gold nanoparticle dose enhanced radiotherapy (GNPT) using X-rays. Br J Radiol. 2016; 89(1059): 20150200.
34.Ghasemi Jangjoo A, Ghiasi H, Mesbahi A. A Monte Carlo study on the radio-sensitization effect of gold nanoparticles in brachytherapy of prostate by 103Pd seeds. PJMPE. 2019; 25: 87-92.
35.Khodadadi A, Nedaie HA, Sadeghi M, Ghassemi MR, Mesbahi A, Banaee N. Determination of the dose enhancement exclusively in tumor tissue due to the presence of GNPs. Appl Radiat Isot. 2019; 145: 39-46.
36.Mesbahi A. A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer. Rep Pract Oncol Radiother. 2010; 15(6): 176-180.
37.Mesbahi A, Jamali F, Garehaghaji N. Effect of photon beam energy, gold nanoparticle size and concentration on the dose enhancement in radiation therapy. Bioimpacts. 2013; 3(1): 29-35.
38.Hossain M, Su M. Nanoparticle Location and Material-Dependent Dose Enhancement in X-ray Radiation Therapy. J Phys Chem C. 2012; 116(43): 23047-23052.
39.Lee C, Cheng NN, Davidson RA, Guo T. Geometry Enhancement of Nanoscale Energy Deposition by X-rays. J Phys Chem C. 2012; 116(20): 11292-11297.
40.Paro AD, Hossain M, Webster TJ, Su M. Monte Carlo and analytic simulations in nanoparticle-enhanced radiation therapy. Int J Nanomedicine . 2016; 11: 4735-4741.
41.Retif P, Reinhard A, Héna P, Jouan-Hureaux V, Chateau A, Sancey L. Monte Carlo simulations guided by imaging to predict the in vitro ranking of radiosensitizing nanoparticles. Int J Nanosci. 2016;Volume 11.
42.Villagomez-Bernabe B, Currell FJ. Physical Radiation Enhancement Effects Around Clinically Relevant Clusters of Nanoagents in Biological Systems. Sci Rep. 2019; 9(1): 8156-.
43.McMahon SJ, Hyland WB, Muir MF, Coulter JA, Jain S, Butterworth KT. Biological consequences of nanoscale energy deposition near irradiated heavy atom nanoparticles. Sci Rep. 2011; 1.
44.Ngwa W, Makrigiorgos GM, Berbeco RI. Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement. Phys Med Biol. 2010; 55: 6533.
45.Howell RW. Auger processes in the 21st century. Int J Radiat Biol. 2008; 84(12): 959-75.
46.Porcel E, Liehn S, Remita H, Usami N, Kobayashi K, Furusawa Y. Platinum nanoparticles: a promising material for future cancer therapy? Nanotechnology. 2010: 21.
47.Paro A, Hossain M, Webster T, Su M. Monte Carlo and analytic simulations in nanoparticle-enhanced radiation therapy. Int J Nanosci. 2016;Volume 11: 4735-4741.
48.Kong T, Zeng J, Wang X, Yang X, Yang J, McQuarrie S, et al. Enhancement of Radiation Cytotoxicity in Breast-Cancer Cells by Localized Attachment of Gold Nanoparticles. Small (Weinheim an der Bergstrasse, Germany). 2008; 4: 1537-1543.
49.Chithrani DB, Jelveh S, Jalali F, van Prooijen M, Allen C, Bristow RG. Gold nanoparticles as radiation sensitizers in cancer therapy. Radiation research. 2010; 173(6): 719-728.
50.Peukert D, Kempson I, Douglass M, Bezak E. Metallic nanoparticle radiosensitisation of ion radiotherapy: A review. Physica Medica. 2018; 47: 121-128.