Radiosensitization effect of PEGylated Gold Nanoparticles in Orthovoltage X-ray Irradiation of the MCF-7 Cancerous Cell Line

Authors
K. Khoshgard 1
B. Hashemi 2
A. Arbabi 3
M. J. Rasaee 4
M. Soleimani 5
1 Ph.D. Candidate, Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
2 Associated Professor, Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
3 Professor, Department of Radiotherapy, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4 Professor, Department of Medical Biothecnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
5 Associated Professor, Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Abstract
Objective: Due to recent advances in nanotechnology it is now possible to accumulate high atomic-number nanomaterial such as gold nanoparticles (GNPs) in cancerous cells and take advantage of their absorbed dose enhancement property as radiosensitizing agents. This study aimed to investigate the absorbed dose enhancement factor due to the presence of PEGylated GNPs under the irradiation of an MCF-7 cancerous cell line using orthovoltage X-ray beams. Methods: We synthesized GNPs with an average diameter of 47 nm and joined them to polyethylene glycol. A total of 50 μg/mL of the pegylated GNPs were incubated with MCF-7 cells for 1, 2, 6, 12, and 24 hours, after which we compared their cytotoxicities. Then, PEGylated GNPs (50μg/mL) were incubated with MCF-7 cells for 12 and 24 hours and their radiosensitizing effect during 2Gy delivery of 120, 180 and 200 kVp X-ray beams were compared by the MTT assay. Results: Cytotoxicity studies showed no significant effect of GNPs on cell viability. Significant differences in cell survival were observed between the groups irradiated with and without GNPs, which lead to an average absorbed dose enhancement factor of 1.22±0.06. According to the results, there was no radiosensitization difference due to the usage of 120, 180 and 200 kVp X-ray beams. However increased incubation time increased the dose enhancement factor. Conclusion: By using PEGylated GNPs we can decrease the prescribed X-ray dose, yet maintain the same level of cancerous cell killing.

Keywords

[1]     Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol 2009; 20(3): 556-63.
[2]     Andreyev HJ. Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future. Clin Oncol (R Coll Radiol) 2007; 19(10): 790-9.
[3]     Witteles RM. Radiation therapy for breast cancer: buyer beware. J Am Coll Cardiol 2011; 57(4): 453-4.
[4]     Shibamoto Y, Zhou L, Hatta H, Mori M, Nishimoto SI. n vivo evaluation of a novel antitumorprodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), which releases 5-fluorouracil upon hypoxic irradiation. Int J Radiat Oncol Biol Phys 2001; 49(2): 407-13.
[5]     Miyake K, Shimada M, Nishioka M, Sugimoto K, Batmunkh E, Uto Y, Nagasawa H, Hori H. The novel hypoxiccell radiosensitizer, TX-1877 has antitumoractivity through suppression of angiogenesis and inhibits livermetastasis on xenograft model of pancreatic cancer. Cancer Lett 2008; 272(2): 325-35.
[6]     Spiers Fw. The influence of energy absorption and electron range on dosage in irradiated bone. Br J Radiol 1949; 22(261): 521-33.
[7]     Castillo MH, Button TM, Doerr R, Homs MI, Pruett CW, Pearce JI. Effects of radiotherapy on mandibularreconstruction plates. Am J Surg 1988; 156(4): 261-3.
[8]     Shukla R, Bansal V, Chaudhary M, Basu A, Bhonde RR, Sastry M. Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopicoverview. Langmuir 200; 21(23): 10644-54.
[9]     Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small 2008; 4(1): 26-49.
[10]  Boudaïffa B, Cloutier P, Hunting D, Huels MA, Sanche L. Resonant formation of DNA strand breaks by low-energy (3 to 20 eV) electrons. Science 2000; 287(5458): 1658-60.
[11]  Carter JD, Cheng NN, Qu Y, Suarez GD, Guo T. Nanoscale energydeposition by X-rayabsorbing nanostructures. J Phys Chem B 2007; 111(40): 11622-5.
[12]  Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to enhance-radiotherapy in mice. Phys Med Biol 2004; 49(18): N309-15.
[13]  Butterworth KT, Wyer JA, Brennan-Fournet M, Latimer CJ, Shah MB, Currell FJ, Hirst DG. Variation of strand break yield for plasmid DNA irradiated with high-Z metal nano-particles. Radiat Res 2008; 170(3): 381-7.
[14]  Rahman WN, Bishara N, Ackerly T, He CF, Jackson P, Wong C, Davidson R, Geso M. Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy. Nanomedicine 2009; 5(2): 136-42.
[15]  Brun E, Sanche L, Sicard-Roselli C. Parameters governing gold nanoparticle X-ray radio-sensitization of DNA in solution. Colloids Surf B Biointerfaces 2009; 72(1): 128-34.
[16]  Kong T, Zeng J, Wang X, Yang X, Yang J, McQuarrie S, McEwan A, Roa W, Chen J, Xing JZ. Enhancement of radiation cyto-toxicity in breast-cancer cells by localized attachment of gold nanoparticles. Small 2008; 4(9): 1537-43.
[17]  Turkevich J, Stevenson PC, Hillier J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 1951; 11: 55-75.
[18]  Andreo P, Burns DT, Hohlfeld K, Huq MS, Kanai T, Laitano F, Smythe, VG, Vynckier, S. Absorbed dose determination in external beam radiotherapy: An international Code of Practice for dosimetry based on standards of absorbed dose to water. Vienna: IAEA, Technical Reports Series No. 398, 2000.
[19]  Zheng Y, Hunting DJ, Ayotte P, Sanche L. Radiosensitization of DNA by gold nanoparticles irradiated with high-energy electrons. Radiat Res 2008; 169(1): 19-27.
[20]  Chang MY, Shiau AL, Chen YH, Chang CJ, Chen HH, Wu CL. Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice. Cancer Sci 2008; 99(7): 1479-84.
[21]  Roa W, Zhang X, Guo L, Shaw A, Hu X, Xiong Y, Gulavita S, Patel S, Sun X, Chen J, Moore R, Xing JZ. Gold nanoparticlesensitize radiotherapy of prostate cancer cells by regulation of the cell cycle. Nanotechnology 2009; 20(37): 375101.
[22]  Liu CJ, Wang CH, Chen ST, Chen HH, Leng WH, Chien CC, Wang CL, Kempson IM, Hwu Y, Lai TC, Hsiao M, Yang CS, Chen YJ, Margaritondo G. Enhancement of cell radiation sensitivity by pegylatedgold nanoparticles. Phys Med Biol 2010; 55(4): 931-45.
[23]  Chithrani BD, Ghazani AA, Chan WC. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 2006; 6(4): 662-8.
[24]  Biston MC, Joubert A, Adam JF, Elleaume H, Bohic S, Charvet AM, Estève F, Foray N, Balosso J. Cure of Fisherrats bearing radioresistant F98 glioma treated with cis-platinum and irradiated with monochromatic synchrotron X-rays. Cancer Res 2004; 64(7): 2317-23.
Pathobiology Reserach
Volume 15, Issue 3
October 2012
Pages 11-22