Abstract
Background
Gold nanoparticles (GNPs) have been conceived to cause increased cytotoxicity of radiotherapy in human malignant cells. Greater uptake of GNPs by cells may induce increased radiation effects. Here we report the radiosensitization effect of glucose-capped GNPs (Glu-GNPs) with different sizes (16 nm and 49 nm) on MDA-MB-231 cells in the presence of megavoltage X-rays.
Methods
Transmission electron microscopy (TEM) was used to observe the distribution of Glu-GNPs in cells. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used to measure the quantities of Glu-GNPs absorbed by cells. After treatment of Glu-GNPs with a series of concentrations, we used the MTT and clonogenic assays to confirm the radiation enhancement effect of Glu-GNPs on MDA-MB-231 cells. The cell cycle distribution was analyzed by flow cytometry to further explore the mechanisms of enhanced radiosensitivity of Glu-GNPs.
Results
TEM showed that Glu-GNPs are mainly distributed in the cytoplasm of cells, including endosomes and lysosomes. ICP-AES indicates that MDA-MB-231 cells absorb more 49-nm Glu-GNPs than 16-nm Glu-GNPs in number (P < 0.05). Glu-GNPs have little cytotoxicity toward MDA-MB-231 cells with a concentration below 20 nM. In the clonogenic assay, the combination of Glu-GNPs with radiation induced a significant growth inhibition, compared with radiation alone (P < 0.05). Moreover 49-nm Glu-GNPs induced much greater radiation effects than 16-nm Glu-GNPs (P < 0.05). Flow cytometry shows that Glu-GNPs can help radiation arrest more cells in the G2/M phase, with greater effect with 49-nm Glu-GNPs than 16-nm Glu-GNPs.
Conclusions
Glu-GNPs can increase the cytotoxicity of radiation toward MDA-MB-231 cells, probably by regulating the distribution of the cell cycle, with more cells in the G2/M phase. The effect of radiation enhancement may be related to the quantities of Glu-GNPs in the cells.
Similar content being viewed by others
References
Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev. 2009;38(6):1759–82.
Kong T, Zeng J, Wang X, Yang X, Yang J, McQuarrie S, McEwan A, Roa W, Chen J, Xing JZ. Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles. Small. 2008;4(9):1537–43.
Zhang X, Xing JZ, Chen J, Ko L, Amanie J, Gulavita S, Pervez N, Yee D, Moore R, Roa W. Enhanced radiation sensitivity in prostate cancer by gold-nanoparticles. Clin Inv Med. 2008;31(3):E160–7.
Zhang XD, Wu D, Shen X, Chen J, Sun YM, Liu PX, Liang XJ. Size-dependent radiosensitization of PEG-coated gold nanoparticles for cancer radiation therapy. Biomaterials. 2012;33(27):6408–19.
Tsiamas P, Liu B, Cifter F, Ngwa WF, Berbeco RI, Kappas C, Theodorou K, Marcus K, Makrigiorgos MG, Sajo E, Zygmanski P. Impact of beam quality on megavoltage radiotherapy treatment techniques utilizing gold nanoparticles for dose enhancement. Phys Med Biol. 2013;58(3):451–64.
Hainfeld JF, Smilowitz HM, O’Connor MJ, Dilmanian FA, Slatkin DN. Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine (Lond). 2012. doi:10.2217/nnm.12.165
Matsudaira H, Ueno AM, Furuno I. Iodine contrast medium sensitizes cultured mammalian cells to X rays but not to gamma rays. Rad Res. 1980;84(1):144–8.
Chithrani BD, Stewart J, Allen C, Jaffray DA. Intracellular uptake, transport, and processing of nanostructures in cancer cells. Nanomedicine. 2009;5(2):118–27.
Gao H, Shi W, Freund LB. Mechanics of receptor-mediated endocytosis. Proc Natl Acad Sci U S A. 2005;102(27):9469–74.
Yen HJ, Hsu SH, Tsai CL. Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. Small. 2009;5(13):1553–61.
Geng F, Song K, Xing JZ, Yuan C, Yan S, Yang Q, Chen J, Kong B. Thio-glucose bound gold nanoparticles enhance radio-cytotoxic targeting of ovarian cancer. Nanotechnology. 2011;22(28):285101.
Frens G. Controlled nucleation for the regulation of the particles size in monodispersed gold suspensions. Nat Phys Sci. 1973;241:20–2.
Jain S, Coulter JA, Hounsell AR, Butterworth KT, McMahon SJ, Hyland WB, Muir MF, Dickson GR, Prise KM, Currell FJ, O’Sullivan JM, Hirst DG. Cell-specific radiosensitization by gold nanoparticles at megavoltage radiation energies. Int J Rad Oncol Biol Phys. 2011;79(2):531–9.
Chithrani DB, Jelveh S, Jalali F, van Prooijen M, Allen C, Bristow RG, Hill RP, Jaffray DA. Gold nanoparticles as radiation sensitizers in cancer therapy. Rad Res. 2010;173(6):719–28.
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. Can Sci. 2008;99(7):1479–84.
Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol. 2004;49(18):N309–15.
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.
Patra HK, Banerjee S, Chaudhuri U, Lahiri P, Dasgupta AK. Cell selective response to gold nanoparticles. Nanomedicine. 2007;3(2):111–9.
Hainfeld JF, Dilmanian FA, Zhong Z, Slatkin DN, Kalef-Ezra JA, Smilowitz HM. Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma. Phys Med Biol. 2010;55(11):3045–59.
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 nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle. Nanotechnology. 2009;20(37):375101.
Parshad R, Gantt R, Sanford KK, Jones GM. Chromosomal radiosensitivity of human tumor cells during the G2 cell cycle period. Can Res. 1984;44(12 Pt 1):5577–82.
Zampetti-Bosseler F, Scott D. Cell death, chromosome damage and mitotic delay in normal human, ataxia telangiectasia and retinoblastoma fibroblasts after x-irradiation. Int J Rad Biol Relat Stud Phys Chem Med. 1981;39(5):547–58.
Painter RB, Young BR. Radiosensitivity in ataxia-telangiectasia: a new explanation. Proc Natl Acad Sci U S A. 1980;77(12):7315–7.
Chithrani BD, Chan WC. Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett. 2007;7(6):1542–50.
De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJ, Geertsma RE. Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials. 2008;29(12):1912–9.
Acknowledgments
This research was supported by the Laboratory of Hemotology, Qilu Hospital, Shandong University. The authors are grateful for the support of Prof. Dairong Chen (School of Chemistry and Chemical Engineering, Shandong University), for providing instrument and material along with suggestions during the preparation of Glu-GNPs
Conflict of interest
The authors report no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Cuihong Wang and Yuhua Jiang contributed to this work equally.
About this article
Cite this article
Wang, C., Jiang, Y., Li, X. et al. Thioglucose-bound gold nanoparticles increase the radiosensitivity of a triple-negative breast cancer cell line (MDA-MB-231). Breast Cancer 22, 413–420 (2015). https://doi.org/10.1007/s12282-013-0496-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12282-013-0496-9