Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

The Radiosensitivity Effect of Folic Acid Conjugated Gold Nanoparticles in Superficial Radiation Therapy of MCF-7 Cancer Cell Line

Document Type : Research Paper

Authors

K Khoshgard
B Hashemi
A Arbabi
M. J Rasaee
M Soleimani
Abstract
Recent dvances in nanotechnology have enabled us to accumulate high atomic-number nano-materials, such as gold nanoparticles (GNPs), in tumor cells selectively using different techniques and take the advantage of the dose enhancement factor resulting from the presence of such high-Z elements as the vicinity of cancerous cells as a radiosensitizer agent. In this research, the GNPs with an average diameter of 50nm were synthesized and conjugated with folic acid. Different concentrations of this nanoconjugate were incubated with MCF-7 cells for 24 hours and its cytotoxicity was investigated. The results showed that increasing the nanoconjugate concentration up to a critical amount, affects the cells viability. The radiosensitizing effect of the folate nanoconjugate, with a concentration of 50μg/mL, on the MCF-7 cells was assessed under 2Gy of x-ray radiation, generated by an orthhovoltage radiotherapy machine, at various energies of 120, 180, 200 kVp, using the MTT assay. Significant differences in the cell survival were noted among the groups exposed to x-ray radiation with and without the nanoconjugate. A maximum dose enhancement factor of 1.34±0.03 was obtained for the 180kVp X-ray beam. The findings enable us to decrease by one third of the prescribed dose while having the same level of damage to cancer cells. Also, this dose reduction results in lower exposure to the normal tissues located close to the target.

Highlights

  1. I. Harirchi, M. Karbakhsh, A. Kashefi, A. J. Momtahen, Breast cancer in Iran: results of a multi-center study, Asian Pac J Cancer Prev, 5 (2004) 24-27.

 2.   H. J. Andreyev, Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future, Clin Oncol (R Coll Radiol), 19 (2007) 790-799.

  1. Y. Shibamoto, L. Zhou, H. Hatta, M. Mori, S. I. Nishimoto, In vivo evaluation of a novel antitumor prodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), which releases 5-fluorouracil upon hypoxic irradiation, Int J Radiat Oncol Biol Phys, 49 (2001) 407-413.
  2. K. Miyake, M. Shimada, M. Nishioka, K. Sugimoto, E. Batmunkh, Y. Uto, H. Nagasawa, H. Hori, The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity through suppression of angiogenesis and inhibits liver metastasis on xenograft model of pancreatic cancer, Cancer Lett, 272 (2008) 325-335.
  3. F. W. Spiers, The influence of energy absorption and electron range on dosage in irradiated bone, Br J Radiol, 22 (1949) 521-533.
  4. M. H. Castillo, T. M. Button, R. Doerr, M. I. Homs, C. W. Pruett, J. I. Pearce, Effects of radiotherapy on mandibular reconstruction plates, Am J Surg, 156 (1988) 261-263.
  5. J. F. Hainfeld, D. N. Slatkin, H. M. Smilowitz, The use of gold nanoparticles to enhance radiotherapy in mice, Phys Med Biol, 49 (2004) N309-315.
  6. R. Shukla, V. Bansal, M. Chaudhary, A. Basu, R. R. Bhonde, M. Sastry, Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview, Langmuir, 21 (2005) 10644-10654.
  7. N. Lewinski, V. Colvin, R. Drezek, Cytotoxicity of nanoparticles, Small, 4 (2008) 26-49.

10. S. Uehara, H. Nikjoo, D. T. Goodhead, Comparison and assessment of electron cross sections for Monte Carlo track structure codes, Radiat Res, 152 (1999) 202-213.

11. B. Boudaiffa, P. Cloutier, D. Hunting, M. A. Huels, L. Sanche, Resonant formation of DNA strand breaks by low-energy (3 to 20eV) electrons, Science, 287 (2000) 1658-1660.

12. M. Y. Chang, A. L. Shiau, Y. H. Chen, C. J. Chang, H. H. Chen, C. L. Wu, Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice, Cancer Sci, 99 (2008) 1479-1484.

13. S. E. McNeil, Nanotechnology for the biologist, J. Leukoc Biol, 78 (2005) 585-594.

14. T. Kong, J. Zeng, X. Wang, X. Yang, J. Yang, S. McQuarrie, A. McEwan, W. Roa, J. Chen, J. Z. Xing, Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles, Small, 4 (2008) 1537-1543.

15. W. Roa, X. Zhang, L. Guo, A. Shaw, X. Hu, Y. Xiong, S. Gulavita, S. Patel, X. Sun, J. Chen, R. Moore, J. Z. Xing, Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle, Nanotechnology 20 (2009) 375101.

16. J. Sudimack and R. J. Lee, Targeted drug delivery via the folate receptor, Adv Drug Deliv Rev, 41 (2000) 147-162.

17. J. H. van Steenis, E. M. van Maarseveen, F. J. Verbaan, R. Verrijk, D. J. Crommelin, G. Storm, W. E. Hennink, Preparation and characterization of folate-targeted pEG-coated pDMAEMA-based polyplexes, J. Control Release, 87 (2003) 167-176.

 18. H. S. Yoo and T. G. Park, Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin-PEG-folate conjugate, J. Control Release, 100 (2004) 247-256.

19. A. Shakeri-Zadeh, G. A. Mansoori, A. R. Hashemian, H. Eshghi, A. Sazgarnia, A. R. Montazer-Abadi, Cancer cells targeting and destruction using folate conjugated gold nanoparticles, Proc Biotech Mol, 4 (2010) 6-12.

 20. A. Shakeri-Zadeh, M. Ghasemifard, G. A. Mansoori, Structural and Optical Characterization of Folate conjugated Gold Nanoparticle, Physica E, 42 (2010) 1272-1280.

21. P. Andreo, D. T. Burns, K. Hohlfeld, M. S. Huq, T. Kanai, F. Laitano, V. G. Smyth, S. Vynckier, Absorbed dose determination in external beam radiotherapy: An international Code of Practice for dosimetry based on standards of absorbed dose to water, IAEA, Technical Report Serie Vienna, 2000.

22. E. Brun, L. Sanche, C. Sicard-Roselli, Parameters governing gold nanoparticle X-ray radiosensitization of DNA in solution, Colloids Surf B Biointerfaces, 72 (2009) 128-134.

23. M. C. Biston, A. Joubert, J. F. Adam, H. Elleaume, S. Bohic, A. M. Charvet, F. Esteve, N. Foray, J. Balosso, Cure of Fisher rats bearing radioresistant F98 glioma treated with cis-platinum and irradiated with monochromatic synchrotron X-rays, Cancer Res, 64 (2004) 2317-2323.

  24. J. F. Hainfeld, F. A. Dilmanian, D. N. Slatkin, H. M. Smilowitz, Radiotherapy enhancement with gold nanoparticles, J. Pharm Pharmacol, 60 (2008) 977-985.

25. S. Corde, A. Joubert, J. F. Adam, A. M. Charvet, J. F. Le Bas, F. Esteve, H. Elleaume, J. Balosso, Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds, Br. J. Cancer, 91 (2004) 544-551.

26. B. D. Chithrani, A. A. Ghazani, W. C. Chan, Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells, Nano Lett, 6 (2006) 662-668.

27. N. Pernodet, X. Fang, Y. Sun, A. Bakhtina, A. Ramakrishnan, J. Sokolov, A. Ulman, M. Rafailovich, Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts, Small, 2 (2006) 7673-7676.

28. B. D. Chithrani and W. C. Chan, Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes, Nano Lett, 7 (2007) 1542-1550.

Keywords

Radiosensitization
Gold Nanoparticles
Folic Acid
Superficial Radiotherapy
  1. I. Harirchi, M. Karbakhsh, A. Kashefi, A. J. Momtahen, Breast cancer in Iran: results of a multi-center study, Asian Pac J Cancer Prev, 5 (2004) 24-27.

 2.   H. J. Andreyev, Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future, Clin Oncol (R Coll Radiol), 19 (2007) 790-799.

  1. Y. Shibamoto, L. Zhou, H. Hatta, M. Mori, S. I. Nishimoto, In vivo evaluation of a novel antitumor prodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), which releases 5-fluorouracil upon hypoxic irradiation, Int J Radiat Oncol Biol Phys, 49 (2001) 407-413.
  2. K. Miyake, M. Shimada, M. Nishioka, K. Sugimoto, E. Batmunkh, Y. Uto, H. Nagasawa, H. Hori, The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity through suppression of angiogenesis and inhibits liver metastasis on xenograft model of pancreatic cancer, Cancer Lett, 272 (2008) 325-335.
  3. F. W. Spiers, The influence of energy absorption and electron range on dosage in irradiated bone, Br J Radiol, 22 (1949) 521-533.
  4. M. H. Castillo, T. M. Button, R. Doerr, M. I. Homs, C. W. Pruett, J. I. Pearce, Effects of radiotherapy on mandibular reconstruction plates, Am J Surg, 156 (1988) 261-263.
  5. J. F. Hainfeld, D. N. Slatkin, H. M. Smilowitz, The use of gold nanoparticles to enhance radiotherapy in mice, Phys Med Biol, 49 (2004) N309-315.
  6. R. Shukla, V. Bansal, M. Chaudhary, A. Basu, R. R. Bhonde, M. Sastry, Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview, Langmuir, 21 (2005) 10644-10654.
  7. N. Lewinski, V. Colvin, R. Drezek, Cytotoxicity of nanoparticles, Small, 4 (2008) 26-49.

10. S. Uehara, H. Nikjoo, D. T. Goodhead, Comparison and assessment of electron cross sections for Monte Carlo track structure codes, Radiat Res, 152 (1999) 202-213.

11. B. Boudaiffa, P. Cloutier, D. Hunting, M. A. Huels, L. Sanche, Resonant formation of DNA strand breaks by low-energy (3 to 20eV) electrons, Science, 287 (2000) 1658-1660.

12. M. Y. Chang, A. L. Shiau, Y. H. Chen, C. J. Chang, H. H. Chen, C. L. Wu, Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice, Cancer Sci, 99 (2008) 1479-1484.

13. S. E. McNeil, Nanotechnology for the biologist, J. Leukoc Biol, 78 (2005) 585-594.

14. T. Kong, J. Zeng, X. Wang, X. Yang, J. Yang, S. McQuarrie, A. McEwan, W. Roa, J. Chen, J. Z. Xing, Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles, Small, 4 (2008) 1537-1543.

15. W. Roa, X. Zhang, L. Guo, A. Shaw, X. Hu, Y. Xiong, S. Gulavita, S. Patel, X. Sun, J. Chen, R. Moore, J. Z. Xing, Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle, Nanotechnology 20 (2009) 375101.

16. J. Sudimack and R. J. Lee, Targeted drug delivery via the folate receptor, Adv Drug Deliv Rev, 41 (2000) 147-162.

17. J. H. van Steenis, E. M. van Maarseveen, F. J. Verbaan, R. Verrijk, D. J. Crommelin, G. Storm, W. E. Hennink, Preparation and characterization of folate-targeted pEG-coated pDMAEMA-based polyplexes, J. Control Release, 87 (2003) 167-176.

 18. H. S. Yoo and T. G. Park, Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin-PEG-folate conjugate, J. Control Release, 100 (2004) 247-256.

19. A. Shakeri-Zadeh, G. A. Mansoori, A. R. Hashemian, H. Eshghi, A. Sazgarnia, A. R. Montazer-Abadi, Cancer cells targeting and destruction using folate conjugated gold nanoparticles, Proc Biotech Mol, 4 (2010) 6-12.

 20. A. Shakeri-Zadeh, M. Ghasemifard, G. A. Mansoori, Structural and Optical Characterization of Folate conjugated Gold Nanoparticle, Physica E, 42 (2010) 1272-1280.

21. P. Andreo, D. T. Burns, K. Hohlfeld, M. S. Huq, T. Kanai, F. Laitano, V. G. Smyth, S. Vynckier, Absorbed dose determination in external beam radiotherapy: An international Code of Practice for dosimetry based on standards of absorbed dose to water, IAEA, Technical Report Serie Vienna, 2000.

22. E. Brun, L. Sanche, C. Sicard-Roselli, Parameters governing gold nanoparticle X-ray radiosensitization of DNA in solution, Colloids Surf B Biointerfaces, 72 (2009) 128-134.

23. M. C. Biston, A. Joubert, J. F. Adam, H. Elleaume, S. Bohic, A. M. Charvet, F. Esteve, N. Foray, J. Balosso, Cure of Fisher rats bearing radioresistant F98 glioma treated with cis-platinum and irradiated with monochromatic synchrotron X-rays, Cancer Res, 64 (2004) 2317-2323.

  24. J. F. Hainfeld, F. A. Dilmanian, D. N. Slatkin, H. M. Smilowitz, Radiotherapy enhancement with gold nanoparticles, J. Pharm Pharmacol, 60 (2008) 977-985.

25. S. Corde, A. Joubert, J. F. Adam, A. M. Charvet, J. F. Le Bas, F. Esteve, H. Elleaume, J. Balosso, Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds, Br. J. Cancer, 91 (2004) 544-551.

26. B. D. Chithrani, A. A. Ghazani, W. C. Chan, Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells, Nano Lett, 6 (2006) 662-668.

27. N. Pernodet, X. Fang, Y. Sun, A. Bakhtina, A. Ramakrishnan, J. Sokolov, A. Ulman, M. Rafailovich, Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts, Small, 2 (2006) 7673-7676.

28. B. D. Chithrani and W. C. Chan, Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes, Nano Lett, 7 (2007) 1542-1550.

Journal of Nuclear Science, Engineering and Technology (JONSAT)
Volume 34, Issue 2 - Serial Number 64
September 2012
Pages 38-47

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