, Volume 3, Issue 2, pp 116–126 | Cite as

Analysis of Potential Radiosensitizing Materials for X-Ray-Induced Photodynamic Therapy

  • Junko Takahashi
  • Masaki Misawa


For a development of deep tumor treatment in photodynamic therapy, a feasibility of novel radiosensitizers induced by x-ray was investigated. The sensitizers are designed to generate reactive oxygen species (ROS) inside or outside the cell, possibly leading to damage exclusively on tumor cells and reservation of normal cells along the x-ray path. Taking note of the similarity in energy transfer mechanism in photocatalysts, scintillators, and particulate semiconductors, we chose TiO2, ZnS:Ag, CeF3, and quantum dots (CdTe and CdSe) in particulate form, which contain heavy atoms for efficient absorption of x-rays. A parameter study for x-ray operating conditions showed that in a typical scenario, photons with 20 to 170 keV energy are attenuated by 90% through the region of particle dispersed aqueous solution at varying concentration between 0.01 and 100 wt%. The amount of ROS generation under the exposure of polychromatic x-ray was measured using dihydroethidium reagent which detects an integrated amount of several species. Proportional increase in ROS generation to x-ray dose was observed for varying concentrations of TiO2, ZnS:Ag, CeF3, and CdSe quantum dot dispersions. Then, HeLa cells were mixed with aqueous solutions dispersed with sensitizing materials at a concentration of 3.0 mg/ml and were exposed to x-ray. Their survival fraction obtained by a cell proliferation reagent WST-1 immediately after the irradiation showed insignificant effects of sensitizing materials except at large doses. To enhance the sensitization effect, bio-conjugated CdSe quantum dots were internalized in the cytoplasm up to a concentration of 1.0 ng/ml. The cells were irradiated by x-ray up to 5 Gy, and their survival fraction was measured by the colony forming ability 9 days after irradiation. Survival fraction of the cells treated with quantum dots were less than those without quantum dots for all doses, suggesting that the colony forming ability is impaired by the internalized quantum dots.


photodynamic therapy radiotherapy sensitizer reactive oxygen species x-ray photocatalyst nanoparticles 


  1. 1.
    Henderson BW, Dougherty TJ. Photodynamic therapy. New York: Mercel Dekker; 1992.Google Scholar
  2. 2.
    Dolmans DEJGJ, et al. Nat Rev Cancer. 2003;3(5):380–7.CrossRefGoogle Scholar
  3. 3.
    Brown S, Brown EA, Walker I. Lancet Oncol. 2004;5:497–508.CrossRefGoogle Scholar
  4. 4.
    Cohen L, Schwartz S. Cancer Res. 1966;26:1969.Google Scholar
  5. 5.
    Rotman M, Aziz H, Wasserman T. Chemotherapy and irradiation: principle and practice of radiation oncology. 3rd ed. PA: Lippincot-Raven Publishers; 1997.Google Scholar
  6. 6.
    Wang X, Ohnishi T. J Radiat Res. 1997;38:179–94.CrossRefGoogle Scholar
  7. 7.
    Mauceri HJ, Hanna NN, Beckett MA, et al. Nature. 1998;394:287–91.CrossRefGoogle Scholar
  8. 8.
    Cai R, Kubota Y, Shuin T, Sakai H, Hashimoto K, Fujishima A. Cancer Res. 1992;52:2346.Google Scholar
  9. 9.
    Bakakova R, et al. Nat Biotechnol. 2004;22:1360–1.CrossRefGoogle Scholar
  10. 10.
    Bakalova R, Ohba H, Zhelev Z, Nagase T, Jose R, Ishikawa M, Baba Y. Nano Lett. 2004;4(9):1567–73.CrossRefGoogle Scholar
  11. 11.
    NIST. Standard Reference Database 8 (XGAM), NIST X-Ray and Gamma-Ray Attenuation Coefficients and Cross Sections Database, ver.1.3; 2005.Google Scholar
  12. 12.
    Zuo L, et al. Am J Physiol Cell Physiol. 2000;279:C1058–66.Google Scholar
  13. 13.
    Ollis DF, Al-Ekabi H, Ed. Photocatalytic purification and treatment of water and air. Amsterdam: Elsevier; 1993.Google Scholar
  14. 14.
    Medintz L, Ueda T, Goldman E, Mattoussi H. Nature Materials. 2005;4:435–45.CrossRefGoogle Scholar
  15. 15.
    Elkind MM, Sutton H. Radiat Res. 1966;13(4):556–93.CrossRefGoogle Scholar
  16. 16.
    Kajiwara K, Fujii G, Saito A, Tanihara M. Photon Factory Activity Report 2002, 2003;20B:259.Google Scholar
  17. 17.
    Kobayashi K, Usami N, Maezawa H, Hayashi T, Hieda K, Takakura K. Journal of Biomedical Nanotechnology. 2006;2(2):116–9.CrossRefGoogle Scholar
  18. 18.
    Kobayashi K, Frohlich H, Usami N, Takakura K, LeSech C. Radiat Res. 2002;157:32.CrossRefGoogle Scholar
  19. 19.
    Jaiswal JK, Mattoussi H, Mauro JM, Simon SM. Nat Biotechnol. 2003;21(1):47–51.CrossRefGoogle Scholar
  20. 20.
    Voura EB, Jaiswal JK, Mattoussi H, Simon SM. Nat Med. 2004;10(9):993–8.CrossRefGoogle Scholar
  21. 21.
    Derfus AM, Chan WCW, Bhatia SN. Nano Lett. 2004;4:11–8.CrossRefGoogle Scholar
  22. 22.
    Semmler M, Seitz J, Erbe F, Mayer P, Heyder J, Oberdorster G, Kreyling WG. Inhal Toxicol. 2004;16(6–7):453–9.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Technology Information DepartmentNational Institute of Advanced Industrial Science & Technology (AIST)TsukubaJapan
  2. 2.Institute for Human Science and Biomedical Engineering, Biomedical Sensing and Imaging GroupNational Institute of Advanced Industrial Science & Technology (AIST)TsukubaJapan

Personalised recommendations