Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Gold nanoparticles enhance anti-tumor effect of radiotherapy to hypoxic tumor

  • Kim, Mi Sun (Department of Radiation Oncology, Yonsei University College of Medicine) ;
  • Lee, Eun-Jung (Department of Radiation Oncology, Yonsei University College of Medicine) ;
  • Kim, Jae-Won (Department of Radiation Oncology, Yonsei University College of Medicine) ;
  • Chung, Ui Seok (Department of Chemical and Biomolecular Engineering, Yonsei University) ;
  • Koh, Won-Gun (Department of Chemical and Biomolecular Engineering, Yonsei University) ;
  • Keum, Ki Chang (Department of Radiation Oncology, Yonsei University College of Medicine) ;
  • Koom, Woong Sub (Department of Radiation Oncology, Yonsei University College of Medicine)
  • Received : 2016.05.07
  • Accepted : 2016.08.02
  • Published : 2016.09.30
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Abstract

Purpose: Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Materials and Methods: Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Results: Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. Conclusion: In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

Keywords

References

  1. Harris AL. Hypoxia: a key regulatory factor in tumour growth. Nat Rev Cancer 2002;2:38-47. https://doi.org/10.1038/nrc704
  2. Overgaard J. Hypoxic modification of radiotherapy in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis. Radiother Oncol 2011;100:22-32. https://doi.org/10.1016/j.radonc.2011.03.004
  3. Harada H. How can we overcome tumor hypoxia in radiation therapy? J Radiat Res 2011;52:545-56. https://doi.org/10.1269/jrr.11056
  4. Barker HE, Paget JT, Khan AA, Harrington KJ. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer 2015;15:409-25. https://doi.org/10.1038/nrc3958
  5. Semenza GL. Intratumoral hypoxia, radiation resistance, and HIF-1. Cancer Cell 2004;5:405-6. https://doi.org/10.1016/S1535-6108(04)00118-7
  6. Han G, Ghosh P, Rotello VM. Functionalized gold nanoparticles for drug delivery. Nanomedicine (Lond) 2007;2:113-23. https://doi.org/10.2217/17435889.2.1.113
  7. Zhao Y, Yu B, Hu H, Hu Y, Zhao NN, Xu FJ. New low molecular weight polycation-based nanoparticles for effective codelivery of pDNA and drug. ACS Appl Mater Interfaces 2014;6:17911-9. https://doi.org/10.1021/am5046179
  8. Qian X, Peng XH, Ansari DO, et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat Biotechnol 2008;26:83-90. https://doi.org/10.1038/nbt1377
  9. Perrault SD, Walkey C, Jennings T, Fischer HC, Chan WC. Mediating tumor targeting efficiency of nanoparticles through design. Nano Lett 2009;9:1909-15. https://doi.org/10.1021/nl900031y
  10. Conde J, Rosa J, de la Fuente JM, Baptista PV. Goldnanobeacons for simultaneous gene specific silencing and intracellular tracking of the silencing events. Biomaterials 2013;34:2516-23. https://doi.org/10.1016/j.biomaterials.2012.12.015
  11. Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 2004;49:N309-15. https://doi.org/10.1088/0031-9155/49/18/N03
  12. 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. https://doi.org/10.1177/153303460700600504
  13. 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. https://doi.org/10.1088/0031-9155/54/16/004
  14. Rahman WN, Bishara N, Ackerly T, et al. Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy. Nanomedicine 2009;5:136-42. https://doi.org/10.1016/j.nano.2009.01.014
  15. Kojima C, Hirano Y, Yuba E, Harada A, Kono K. Preparation and characterization of complexes of liposomes with gold nanoparticles. Colloids Surf B Biointerfaces 2008;66:246-52. https://doi.org/10.1016/j.colsurfb.2008.06.022
  16. 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. https://doi.org/10.1016/j.ijrobp.2010.10.022
  17. Retif P, Pinel S, Toussaint M, et al. Nanoparticles for radiation therapy enhancement: the key parameters. Theranostics 2015;5:1030-44. https://doi.org/10.7150/thno.11642
  18. Chung US, Kim JH, Kim B, Kim E, Jang WD, Koh WG. Dendrimer porphyrin-coated gold nanoshells for the synergistic combination of photodynamic and photothermal therapy. Chem Commun (Camb) 2016;52:1258-61. https://doi.org/10.1039/C5CC09149G
  19. Hall EJ, Giaccia AJ. Oxygen effect and reoxygenation. In: Hall EJ, Giaccia AJ, editors. Radiobiology for the radiologist. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012. p. 86-103.
  20. Bindra RS, Crosby ME, Glazer PM. Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev 2007;26:249-60. https://doi.org/10.1007/s10555-007-9061-3
  21. Park HJ, Griffin RJ, Hui S, Levitt SH, Song CW. Radiationinduced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res 2012;177:311-27. https://doi.org/10.1667/RR2773.1
  22. Butterworth KT, Coulter JA, Jain S, et al. Evaluation of cytotoxicity and radiation enhancement using 1.9 nm gold particles: potential application for cancer therapy. Nanotechnology 2010;21:295101. https://doi.org/10.1088/0957-4484/21/29/295101
  23. Butterworth KT. Radiosensitization by gold nanoparticles: effective at megavoltage energies and potential role of oxidative stress. Transl Cancer Res 2013;2:269-79.
  24. Misawa M, Takahashi J. Generation of reactive oxygen species induced by gold nanoparticles under x-ray and UV Irradiations. Nanomedicine 2011;7:604-14. https://doi.org/10.1016/j.nano.2011.01.014
  25. Ngwa W, Kumar R, Sridhar S, et al. Targeted radiotherapy with gold nanoparticles: current status and future perspectives. Nanomedicine (Lond) 2014;9:1063-82. https://doi.org/10.2217/nnm.14.55
  26. Hagtvet E, Roe K, Olsen DR. Liposomal doxorubicin improves radiotherapy response in hypoxic prostate cancer xenografts. Radiat Oncol 2011;6:135. https://doi.org/10.1186/1748-717X-6-135

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