Document Type : Original Article

Authors

1 Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran

2 Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran

3 Pharmaceutical Department, Food & Drug Laboratory Research Center, Food & Drug Organization (FDO), Tehran, Iran.

4 Nanobiomaterials Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 141761411, Iran

5 Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Numerous unique characteristics of the nanosized gold, including high atomic number, low toxicity, and high biocompatibility make it one of the most appropriate nanostructures to boost radiotherapy efficacy. Many in-vivo and in-vitro investigations have indicated that gold nanoparticles (AuNPs) can significantly increase tumor injuries in low kilovoltage radiotherapy. While deep-lying tumors require much higher energy levels with greater penetration power, and investigations carried out in megavoltage energy range show contradictory results.
Objective: In this study, we quantitatively assess and compare dose enhancement factors (DEFs) obtained through AuNPs under radiation of Cobalt-60 source (1.25MeV) versus Iridium-192 source (380 KeV) using MAGAT gel dosimeter.
Material and Methods: MAGAT polymer gel in both pure and combined with 0.2 mM AuNPs was synthesized. In order to quantify the effect of energy on DEF, irradiation was carried out by Co-60 external radiotherapy and Ir-192 internal radiotherapy. Finally, readings of irradiated and non-irradiated gels were performed by MR imaging.
Results: The radiation-induced R2 (1/T2) changes of the gel tubes doped with AuNPs compared to control samples, upon irradiation of beams released by Ir-192 source showed a significant dose enhancement (15.31% ±0.30) relative to the Co-60 external radiotherapy (5.85% ±0.14).
Conclusion: This preliminary study suggests the feasibility of using AuNPs in radiation therapy (RT), especially in low-energy sources of brachytherapy. In addition, MAGAT polymer gel, as a powerful dosimeter, could be used for 3D visualization of radiation dose distribution of AuNPs in radiotherapy.

Keywords

  1. Detappe A, Kunjachan S, Sancey L, Motto-Ros V, Biancur D, Drane P, et al. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy. J Control Release. 2016;238:103-13. doi: 10.1016/j.jconrel.2016.07.021. PubMed PMID: 27423325.
  2. Moding EJ, Kastan MB, Kirsch DG. Strategies for optimizing the response of cancer and normal tissues to radiation. Nat Rev Drug Discov. 2013;12:526-42. doi: 10.1038/nrd4003. PubMed PMID: 23812271; PubMed Central PMCID: PMC3906736.
  3. Satterlee AB, Yuan H, Huang L. A radio-theranostic nanoparticle with high specific drug loading for cancer therapy and imaging. J Control Release. 2015;217:170-82. doi: 10.1016/j.jconrel.2015.08.048. PubMed PMID: 26341695; PubMed Central PMCID: PMC4640695.
  4. Butterworth KT, McMahon SJ, Currell FJ, Prise KM. Physical basis and biological mechanisms of gold nanoparticle radiosensitization. Nanoscale. 2012;4:4830-8. doi: 10.1039/c2nr31227a. PubMed PMID: 22767423.
  5. Hossain M, Su M. Nanoparticle location and material dependent dose enhancement in X-ray radiation therapy. J Phys Chem C Nanomater Interfaces. 2012;116:23047-52. doi: 10.1021/jp306543q. PubMed PMID: 23393610; PubMed Central PMCID: PMC3563421.
  6. Zhang XD, Wu D, Shen X, Chen J, Sun YM, Liu PX, et al. Size-dependent radiosensitization of PEG-coated gold nanoparticles for cancer radiation therapy. Biomaterials. 2012;33:6408-19. doi: 10.1016/j.biomaterials.2012.05.047. PubMed PMID: 22681980.
  7. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008;60:1615-26. doi: 10.1016/j.addr.2008.08.005. PubMed PMID: 18840489.
  8. Detappe A, Tsiamas P, Ngwa W, Zygmanski P, Makrigiorgos M, Berbeco R. The effect of flattening filter free delivery on endothelial dose enhancement with gold nanoparticles. Med Phys. 2013;40:031706. doi: 10.1118/1.4791671. PubMed PMID: 23464301; PubMed Central PMCID: PMC3585757.
  9. Cho SH, Jones BL, Krishnan S. The dosimetric feasibility of gold nanoparticle-aided radiation therapy (GNRT) via brachytherapy using low-energy gamma-/x-ray sources. Phys Med Biol. 2009;54:4889-905. doi: 10.1088/0031-9155/54/16/004. PubMed PMID: 19636084; PubMed Central PMCID: PMC3064075.
  10. Jones BL, Krishnan S, Cho SH. Estimation of microscopic dose enhancement factor around gold nanoparticles by Monte Carlo calculations. Med Phys. 2010;37:3809-16. doi: 10.1118/1.3455703. PubMed PMID: 20831089.
  11. 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 Biol Phys. 2011;81:270-6. doi: 10.1016/j.ijrobp.2010.10.022. PubMed PMID: 21163591.
  12. Ngwa W, Makrigiorgos GM, Berbeco RI. Gold nanoparticle-aided brachytherapy with vascular dose painting: estimation of dose enhancement to the tumor endothelial cell nucleus. Med Phys. 2012;39:392-8. doi: 10.1118/1.3671905. PubMed PMID: 22225308.
  13. Lechtman E, Chattopadhyay N, Cai Z, Mashouf S, Reilly R, Pignol JP. Implications on clinical scenario of gold nanoparticle radiosensitization in regards to photon energy, nanoparticle size, concentration and location. Phys Med Biol. 2011;56:4631-47. doi: 10.1088/0031-9155/56/15/001. PubMed PMID: 21734337.
  14. 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;38:624-31. doi: 10.1118/1.3539623. PubMed PMID: 21452700.
  15. Herold DM, Das IJ, Stobbe CC, Iyer RV, Chapman JD. Gold microspheres: a selective technique for producing biologically effective dose enhancement. Int J Radiat Biol. 2000;76:1357-64. PubMed PMID: 11057744.
  16. Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol. 2004;49:N309-15. PubMed PMID: 15509078.
  17. Chithrani BD, Ghazani AA, Chan WC. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006;6:662-8. doi: 10.1021/nl052396o. PubMed PMID: 16608261.
  18. Chithrani DB, Jelveh S, Jalali F, van Prooijen M, Allen C, Bristow RG, et al. Gold nanoparticles as radiation sensitizers in cancer therapy. Radiat Res. 2010;173:719-28. doi: 10.1667/RR1984.1. PubMed PMID: 20518651.
  19. Zhang XD, Wu D, Shen X, Chen J, Sun YM, Liu PX, et al. Size-dependent radiosensitization of PEG-coated gold nanoparticles for cancer radiation therapy. Biomaterials. 2012;33:6408-19. doi: 10.1016/j.biomaterials.2012.05.047. PubMed PMID: 22681980.
  20. Fenart L, Casanova A, Dehouck B, Duhem C, Slupek S, Cecchelli R, et al. Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier. J Pharmacol Exp Ther. 1999;291:1017-22.
  21. 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;38:624-31. doi: 10.1118/1.3539623. PubMed PMID: 21452700.
  22. Hauck TS, Ghazani AA, Chan WC. Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. Small. 2008;4:153-9. doi: 10.1002/smll.200700217. PubMed PMID: 18081130.
  23. Alkilany AM, Nagaria PK, Hexel CR, Shaw TJ, Murphy CJ, Wyatt MD. Cellular uptake and cytotoxicity of gold nanorods: molecular origin of cytotoxicity and surface effects. Small. 2009;5:701-8. doi: 10.1002/smll.200801546. PubMed PMID: 19226599.
  24. Cho EC, Liu Y, Xia Y. A simple spectroscopic method for differentiating cellular uptakes of gold nanospheres and nanorods from their mixtures. Angew Chem Int Ed Engl. 2010;49:1976-80. doi: 10.1002/anie.200906584. PubMed PMID: 20146292; PubMed Central PMCID: PMC3359148.
  25. Au L, Zhang Q, Cobley CM, Gidding M, Schwartz AG, Chen J, et al. Quantifying the cellular uptake of antibody-conjugated Au nanocages by two-photon microscopy and inductively coupled plasma mass spectrometry. AcS nano. 2009;4:35-42.doi: 10.1021/nn901392m.
  26. 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;3:29-35. doi: 10.5681/bi.2013.002. PubMed PMID: 23678467; PubMed Central PMCID: PMC3648909.
  27. Alkilany AM, Murphy CJ. Toxicity and cellular uptake of gold nanoparticles: what we have learned so far? J Nanopart Res. 2010;12:2313-33. doi: 10.1007/s11051-010-9911-8. PubMed PMID: 21170131; PubMed Central PMCID: PMC2988217.
  28. Gatoo MA, Naseem S, Arfat MY, Dar AM, Qasim K, Zubair S. Physicochemical properties of nanomaterials: implication in associated toxic manifestations. Biomed Res Int. 2014;2014:498420. doi: 10.1155/2014/498420. PubMed PMID: 25165707; PubMed Central PMCID: PMC4140132.
  29. Villiers C, Freitas H, Couderc R, Villiers MB, Marche P. Analysis of the toxicity of gold nano particles on the immune system: effect on dendritic cell functions. J Nanopart Res. 2010;12:55-60. doi: 10.1007/s11051-009-9692-0. PubMed PMID: 21841911; PubMed Central PMCID: PMC3155055.
  30. Pan Y, Leifert A, Ruau D, Neuss S, Bornemann J, Schmid G, et al. Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. Small. 2009;5:2067-76. doi: 10.1002/smll.200900466. PubMed PMID: 19642089.
  31. Rahman WN, Bishara N, Ackerly T, He CF, Jackson P, Wong C, et al. Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy. Nanomedicine. 2009;5:136-42. PubMed PMID: 19480049.
  32. 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. 2008;4:1537-43. doi: 10.1002/smll.200700794. PubMed PMID: 18712753.
  33. Apanasevich V, Avramenko V, Lukyanov P, Lagureva A, Polkovnikova A, Lukyanenko K, et al. Enhance the absorption of gamma-ray energy inside the tumor using gold nanoparticles and iodine particles. Cancer and Oncology Research. 2014;2:17-20.
  34. Amirrashedi M, Mostaar A, Haghgoo S, Gorji E, Jaberi R, editors. Dose Enhancement in Radiotherapy by Novel Application Of Gadolinium Based MRI Contrast Agent Nanomagnetic Particles in Gel Dosimetry. Toronto: World Congress on Medical Physics and Biomedical Engineering; June 7-12, 2015.
  35. Rahman WN, Wong CJ, Ackerly T, Yagi N, Geso M. Polymer gels impregnated with gold nanoparticles implemented for measurements of radiation dose enhancement in synchrotron and conventional radiotherapy type beams. Australas Phys Eng Sci Med. 2012;35:301-9. doi: 10.1007/s13246-012-0157-x. PubMed PMID: 22892958.
  36. Maggiorella L, Barouch G, Devaux C, Pottier A, Deutsch E, Bourhis J, et al. Nanoscale radiotherapy with hafnium oxide nanoparticles. Future Oncol. 2012;8:1167-81. doi: 10.2217/fon.12.96. PubMed PMID: 23030491.
  37. Sabbaghizadeh R, Shamsudin R, Deyhimihaghighi N, Sedghi A. Enhancement of Dose Response and Nuclear Magnetic Resonance Image of PAGAT Polymer Gel Dosimeter by Adding Silver Nanoparticles. PLoS One. 2017;12:e0168737. doi: 10.1371/journal.pone.0168737. PubMed PMID: 28060829; PubMed Central PMCID: PMC5218462.
  38. Deyhimihaghighi N, Noor NM, Soltani N, Jorfi R, Haghir ME, Adenan M, et al., editors. Contrast enhancement of magnetic resonance imaging (MRI) of polymer gel dosimeter by adding Platinum nano-particles. Vol. 546. Journal of Physics: Conference Series; 2014.
  39. Ezzati AO, Mahdavi SR, Anijdan HM. Size Effects of Gold and Iron Nanoparticles on Radiation Dose Enhancement in Brachytherapy and Teletherapy: A Monte Carlo Study. Iranian Journal of Medical Physics. 2014;11:253-9.
  40. Kakade NR, Sharma SD. Dose enhancement in gold nanoparticle-aided radiotherapy for the therapeutic photon beams using Monte Carlo technique. J Cancer Res Ther. 2015;11:94-7. doi: 10.4103/0973-1482.147691. PubMed PMID: 25879344.
  41. Bahreyni Toossi MT, Ghorbani M, Mehrpouyan M, Akbari F, Sobhkhiz Sabet L, Soleimani Meigooni A. A Monte Carlo study on tissue dose enhancement in brachytherapy: a comparison between gadolinium and gold nanoparticles. Australas Phys Eng Sci Med. 2012;35:177-85. doi: 10.1007/s13246-012-0143-3. PubMed PMID: 22700179.
  42. Hurley C, Venning A, Baldock C. A study of a normoxic polymer gel dosimeter comprising methacrylic acid, gelatin and tetrakis (hydroxymethyl) phosphonium chloride (MAGAT). Appl Radiat Isot. 2005;63:443-56. doi: 10.1016/j.apradiso.2005.03.014. PubMed PMID: 16026995.
  43. De Deene Y, Vergote K, Claeys C, De Wagter C. The fundamental radiation properties of normoxic polymer gel dosimeters: a comparison between a methacrylic acid based gel and acrylamide based gels. Phys Med Biol. 2006;51:653-73. doi: 10.1088/0031-9155/51/3/012. PubMed PMID: 16424587.
  44. Fernandes JP, Pastorello BF, de Araujo DB, Baffa O. Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity. Phys Med Biol. 2008;53:N53-8. doi: 10.1088/0031-9155/53/4/N04. PubMed PMID: 18263941.
  45. Geso M, Ackerly T, Brown S, Chua Z, He C, Wong CJ, et al. Determination of dosimetric perturbations caused by aneurysm clip in stereotactic radiosurgery using gel phantoms and EBT-Gafchromic films. Med Phys. 2008;35:744-52. doi: 10.1118/1.2828200. PubMed PMID: 18383696.
  46. Baldock C, De Deene Y, Doran S, Ibbott G, Jirasek A, Lepage M, et al. Polymer gel dosimetry. Phys Med Biol. 2010;55:R1-63. doi: 10.1088/0031-9155/55/5/R01. PubMed PMID: 20150687; PubMed Central PMCID: PMC3031873.
  47. Chen D, Chung M-B, Shih T-C, Lian J, Chen Y. MAGAT Gel dosimetry validation in RapidArcTM treatment using Cone-beam CT. J Med Biol Eng In Press Accessed. 2012.
  48. Alqathami M, Blencowe A, Geso M, Ibbott G. Quantitative 3D Determination of Radiosensitization by Bismuth-Based Nanoparticles. J Biomed Nanotechnol. 2016;12:464-71. PubMed PMID: 27280244.
  49. Ngwa W, Kumar R, Sridhar S, Korideck H, Zygmanski P, Cormack RA, et al. Targeted radiotherapy with gold nanoparticles: current status and future perspectives. Nanomedicine (Lond). 2014;9:1063-82. doi: 10.2217/nnm.14.55. PubMed PMID: 24978464; PubMed Central PMCID: PMC4143893.
  50. Khan FM. The physics of radiation therapy. Vol. 3. Philadelphia: Lippincott Williams & Wilkins; 2003.
  51. Berger M, Hubbell J, Seltzer S, Chang J, Coursey J, Sukumar R, et al. XCOM: Photon cross sections database, 1998. NIST standard reference database. 1990;8.
  52. Khosravi H, Hashemi B, Mahdavi S, Hejazi P. Effect of gold nanoparticles on prostate dose distribution under Ir-192 internal and 18 MV external radiotherapy procedures using gel dosimetry and monte carlo method. Journal of biomedical physics & engineering. 2015;5:3.
  53. Zhang DG, Feygelman V, Moros EG, Latifi K, Zhang GG. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy. PLoS One. 2014;9:e109389. doi: 10.1371/journal.pone.0109389. PubMed PMID: 25275550; PubMed Central PMCID: PMC4183586.
  54. Marques T, Schwarcke M, Garrido C, Zucolot V, Baffa O, Nicolucci P, editors. Gel dosimetry analysis of gold nanoparticle application in kilovoltage radiation therapy. Journal of Physics: Conference Series; 2010: IOP Publishing.
  55. Roeske JC, Nunez L, Hoggarth M, Labay E, Weichselbaum RR. Characterization of the theorectical radiation dose enhancement from nanoparticles. Technol Cancer Res Treat. 2007;6:395-401. doi: 10.1177/153303460700600504. PubMed PMID: 17877427.
  56. Huang Y-R, Chang Y-J, Hsieh L-L, Liu M-H, Liu J-S, Chu C-H, et al. Dosimetry study of diagnostic X-ray using doped iodide normoxic polymer gels. Radiation Physics and Chemistry. 2014;104:414-9.doi: 10.1016/j.radphyschem.2013.12.014.
  57. Venning AJ, Nitschke KN, Keall PJ, Baldock C. Radiological properties of normoxic polymer gel dosimeters. Med Phys. 2005;32:1047-53. doi: 10.1118/1.1881812. PubMed PMID: 15895589.
  58. Sellakumar P, Samuel EJJ, Supe SS. Water equivalence of polymer gel dosimeters. Radiation Physics and Chemistry. 2007;76:1108-15. Doi: 10.1016/j.radphyschem.2007.03.003.
  59. Lin MH, Huang TC, Kao MJ, Wu J, Chen CL, Wu TH. Three-dimensional dosimetry in brachytherapy: A MAGAT study. Appl Radiat Isot. 2009;67:1432-7. doi: 10.1016/j.apradiso.2009.02.072. PubMed PMID: 19303785.