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Modulation of cancer cells’ radiation response in the presence of folate conjugated Au@Fe2O3 nanocomplex as a targeted radiosensitizer

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Abstract

Objectives

To investigate the effects of Au@Fe2O3 core–shell nanoparticle (NP), with and without conjugation to folic acid (FA) as a targeting ligand, on radiosensitization of both cancer and healthy cells.

Methods

Au@Fe2O3 NPs were first synthesized, then modified with FA, and finally characterized. Radiation dose enhancement studies were performed on KB cancer cells and L929 healthy cells. NPs at the concentration of 20 µg/ml were first incubated with both cell lines and then different doses of 6 MV X-ray radiation were examined. The end effects were evaluated via MTT assay and flow cytometry using AnnexinV/PI kit.

Results

It was indicated that viability of KB cells has a much lower rate than L929 cells when the cells were treated by {(FA-Au@Fe2O3) + (X-ray)} regimen. Cell viability was even decreased significantly when X-ray dose increased. Moreover, flow cytometry studies revealed that FA-targeted NPs induced higher level of apoptosis for KB cancer cells than L929 healthy cells.

Conclusion

Our findings provide a new perspective on high ability of the synthesized FA-targeted Au@Fe2O3 NPs which may be considered as an efficient radiosensitizer in the process of targeted radiation therapy of cancer.

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References

  1. Lin J, Chen X, Huang P. Graphene-based nanomaterials for bioimaging. Adv Drug Deliv Rev. 2016;105:242–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ryu JH, Lee S, Son S, Kim SH, Leary JF, Choi K, et al. Theranostic nanoparticles for future personalized medicine. J Control Release. 2014;190:477–84.

    Article  CAS  PubMed  Google Scholar 

  3. Wang C, Jiang Y, Li X, Hu L. Thioglucose-bound gold nanoparticles increase the radiosensitivity of a triple-negative breast cancer cell line (MDA-MB-231). Breast Cancer. 2015;22(4):413–20.

    Article  PubMed  Google Scholar 

  4. Liu J, Yang Y, Zhu W, Yi X, Dong Z, Xu X, et al. Nanoscale metal − organic frameworks for combined photodynamic & radiation therapy in cancer treatment. Biomaterials. 2016;97:1–9.

    Article  CAS  PubMed  Google Scholar 

  5. Deng Y, Li E, Cheng X, Zhu J, Lu S, Ge C, et al. Facile preparation of hybrid core–shell nanorods for photothermal and radiation combined therapy. Nanoscale. 2016;8(7):3895–9.

    Article  CAS  PubMed  Google Scholar 

  6. Kumar A, Zhang X, Liang X-J. Gold nanoparticles: emerging paradigm for targeted drug delivery system. Biotechnol Adv. 2013;31(5):593–606.

    Article  CAS  PubMed  Google Scholar 

  7. Rana S, Bajaj A, Mout R, Rotello VM. Monolayer coated gold nanoparticles for delivery applications. Adv Drug Deliv Rev. 2012;64(2):200–16.

    Article  CAS  PubMed  Google Scholar 

  8. Al Zaki A, Cormode D, Tsourkas A, Dorsey JF. Increasing the therapeutic efficacy of radiotherapy using nanoparticles. Increasing the therapeutic ratio of radiotherapy. Berlin: Springer; 2017. p. 241–65.

    Book  Google Scholar 

  9. Her S, Jaffray DA, Allen C. Gold nanoparticles for applications in cancer radiotherapy: mechanisms and recent advancements. Advanced drug delivery reviews. 2017;109:84–101.

    Article  CAS  PubMed  Google Scholar 

  10. Shakeri-Zadeh A, Shiran M-B, Khoee S, Sharifi AM, Ghaznavi H, Khoei S. A new magnetic nanocapsule containing 5-fluorouracil: in vivo drug release, anti-tumor, and pro-apoptotic effects on CT26 cells allograft model. J Biomater Appl. 2014;29(4):548–56.

    Article  CAS  PubMed  Google Scholar 

  11. Lucarini M, Franchi P, Pedulli GF, Pengo P, Scrimin P, Pasquato L. EPR study of dialkyl nitroxides as probes to investigate the exchange of solutes between the ligand shell of monolayers of protected gold nanoparticles and aqueous solutions. J Am Chem Soc. 2004;126(30):9326–9.

    Article  CAS  PubMed  Google Scholar 

  12. Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev. 2009;38(6):1759–82.

    Article  CAS  PubMed  Google Scholar 

  13. Beik J, Jafariyan M, Montazerabadi A, Ghadimi-Daresajini A, Tarighi P, Mahmoudabadi A, et al. The benefits of folic acid-modified gold nanoparticles in CT-based molecular imaging: radiation dose reduction and image contrast enhancement. Artif Cells Nanomed Biotechnol. 2017. https://doi.org/10.1080/21691401.2017.1408019.

    Article  PubMed  Google Scholar 

  14. Ghaznavi H, Hosseini-Nami S, Kamrava SK, Irajirad R, Maleki S, Shakeri-Zadeh A, et al. Folic acid conjugated PEG coated gold–iron oxide core–shell nanocomplex as a potential agent for targeted photothermal therapy of cancer. Artif Cells Nanomed Biotechnol. 2017. https://doi.org/10.1080/21691401.2017.1384384.

    Article  PubMed  Google Scholar 

  15. Zeinizade E, Tabei M, Shakeri-Zadeh A, Ghaznavi H, Attaran N, Komeili A, et al. Selective apoptosis induction in cancer cells using folate-conjugated gold nanoparticles and controlling the laser irradiation conditions. Artif Cells Nanomed Biotechnol. 2018. https://doi.org/10.1080/21691401.2018.1443116

    Article  PubMed  Google Scholar 

  16. Zhang X, Xing JZ, Chen J, Ko L, Amanie J, Gulavita S, et al. Enhanced radiation sensitivity in prostate cancer by gold-nanoparticles. Clin Invest Med. 2008;31(3):160–7.

    Article  Google Scholar 

  17. Kong T, Zeng J, Wang X, Yang X, Yang J, McQuarrie S, et al. Enhancement of radiation cytotoxicity in Breast-cancer cells by localized attachment of gold nanoparticles. Small. 2008;4(9):1537–43.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang X-D, Wu D, Shen X, Chen J, Sun Y-M, Liu P-X, et al. Size-dependent radiosensitization of PEG-coated gold nanoparticles for cancer radiation therapy. Biomaterials. 2012;33(27):6408–19.

    Article  CAS  PubMed  Google Scholar 

  19. Hainfeld JF, Smilowitz HM, O’Connor MJ, Dilmanian FA, Slatkin DN. Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine. 2013;8(10):1601–9.

    Article  CAS  PubMed  Google Scholar 

  20. Tsiamas P, Liu B, Cifter F, Ngwa WF, Berbeco RI, Kappas C, et al. Impact of beam quality on megavoltage radiotherapy treatment techniques utilizing gold nanoparticles for dose enhancement. Phys Med Biol. 2013;58(3):451.

    Article  CAS  PubMed  Google Scholar 

  21. Eyvazzadeh N, Shakeri-Zadeh A, Fekrazad R, Amini E, Ghaznavi H, Kamrava SK. Gold-coated magnetic nanoparticle as a nanotheranostic agent for magnetic resonance imaging and photothermal therapy of cancer. Lasers Med Sci. 2017;32(7):1469–77.

    Article  PubMed  Google Scholar 

  22. Wang L, Park H-Y, Stephanie I, Lim I, Schadt MJ, Mott D, et al. Core@ shell nanomaterials: gold-coated magnetic oxide nanoparticles. J Mater Chem. 2008;18(23):2629–35.

    Article  CAS  Google Scholar 

  23. Beik J, Khademi S, Attaran N, Sarkar S, Shakeri-Zadeh A, Ghaznavi H, et al. A nanotechnology-based strategy to increase the efficiency of cancer diagnosis and therapy: folate-conjugated gold nanoparticles. Curr Med Chem. 2017;24(39):4399–416.

    Article  CAS  PubMed  Google Scholar 

  24. Samadian H, Hosseini-Nami S, Kamrava SK, Ghaznavi H, Shakeri-Zadeh A. Folate-conjugated gold nanoparticle as a new nanoplatform for targeted cancer therapy. J Cancer Res Clin Oncol. 2016;142(11):2217–29.

    Article  CAS  PubMed  Google Scholar 

  25. Mirrahimi M, Hosseini V, Kamrava SK, Attaran N, Beik J, Kooranifar S, et al. Selective heat generation in cancer cells using a combination of 808 nm laser irradiation and the folate-conjugated Fe2O3@ Au nanocomplex. Artificial cells, nanomedicine, and biotechnology. 2017:1–13.

  26. Shakeri-Zadeh A, Khoee S, Shiran M-B, Sharifi AM, Khoei S. Synergistic effects of magnetic drug targeting using a newly developed nanocapsule and tumor irradiation by ultrasound on CT26 tumors in BALB/c mice. J Mater Chem B. 2015;3(9):1879–87.

    Article  CAS  Google Scholar 

  27. Sivakumar B, Aswathy RG, Sreejith R, Nagaoka Y, Iwai S, Suzuki M, et al. Bacterial exopolysaccharide based magnetic nanoparticles: a versatile nanotool for cancer cell imaging, targeted drug delivery and synergistic effect of drug and hyperthermia mediated cancer therapy. J Biomed Nanotechnol. 2014;10(6):885–99.

    Article  CAS  PubMed  Google Scholar 

  28. Banu H, Stanley B, Faheem S, Seenivasan R, Premkumar K, Vasanthakumar G. Thermal chemosensitization of breast cancer cells to cyclophosphamide treatment using folate receptor targeted gold nanoparticles. Plasmonics. 2014;9(6):1341–9.

    Article  CAS  Google Scholar 

  29. Beik J, Abed Z, Ghoreishi FS, Hosseini-Nami S, Mehrzadi S, Shakeri-Zadeh A, et al. Nanotechnology in hyperthermia cancer therapy: from fundamental principles to advanced applications. J Control Release. 2016;235:205–21.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    Article  CAS  Google Scholar 

  31. Hu R, Zheng M, Wu J, Li C, Shen D, Yang D, et al. Core-Shell magnetic gold nanoparticles for magnetic field-enhanced radio-photothermal therapy in cervical cancer. Nanomaterials. 2017;7(5):111.

    Article  CAS  PubMed Central  Google Scholar 

  32. Peng X-H, Qian X, Mao H, Wang AY. Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy. Int J Nanomed. 2008;3(3):311.

    CAS  Google Scholar 

  33. Chomoucka J, Drbohlavova J, Huska D, Adam V, Kizek R, Hubalek J. Magnetic nanoparticles and targeted drug delivering. Pharmacol Res. 2010;62(2):144–9.

    Article  CAS  PubMed  Google Scholar 

  34. Wolfe T, Chatterjee D, Lee J, Grant JD, Bhattarai S, Tailor R, et al. Targeted gold nanoparticles enhance sensitization of prostate tumors to megavoltage radiation therapy in vivo. Nanomed Nanotechnol Biol Med. 2015;11(5):1277–83.

    Article  CAS  Google Scholar 

  35. Khoei S, Mahdavi SR, Fakhimikabir H, Shakeri-Zadeh A, Hashemian A. The role of iron oxide nanoparticles in the radiosensitization of human prostate carcinoma cell line DU145 at megavoltage radiation energies. Int J Radiat Biol. 2014;90(5):351–6.

    Article  CAS  PubMed  Google Scholar 

  36. Khoshgard K, Hashemi B, Arbabi A, Rasaee MJ, Soleimani M. Radiosensitization effect of folate-conjugated gold nanoparticles on HeLa cancer cells under orthovoltage superficial radiotherapy techniques. Phys Med Biol. 2014;59(9):2249.

    Article  CAS  PubMed  Google Scholar 

  37. Gao B, Shen L, He K-W, Xiao W-H. GNRs@ SiO2-FA in combination with radiotherapy induces the apoptosis of HepG2 cells by modulating the expression of apoptosis-related proteins. Int J Mol Med. 2015;36(5):1282–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Neshastehriz A, Tabei M, Maleki S, Eynali S, Shakeri-Zadeh A. Photothermal therapy using folate conjugated gold nanoparticles enhances the effects of 6MV X-ray on mouth epidermal carcinoma cells. J Photochem Photobiol, B. 2017;172:52–60.

    Article  CAS  Google Scholar 

  39. Wyllie AH, Kerr JR, Currie A. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306.

    Article  CAS  PubMed  Google Scholar 

  40. Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys. 1995;33(4):781–96.

    Article  CAS  PubMed  Google Scholar 

  41. Cohen-Jonathan E, Bernhard EJ, McKenna WG. How does radiation kill cells? Curr Opin Chem Biol. 1999;3(1):77–83.

    Article  CAS  Google Scholar 

  42. Chiou S-K, Rao L, White E. Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol. 1994;14(4):2556–63.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Igney FH, Krammer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2002;2(4):277–88.

    Article  CAS  Google Scholar 

  44. Li P, Y-w S, Li B-x X, W-c SZ-l, Zhou C, et al. Photo-thermal effect enhances the efficiency of radiotherapy using Arg-Gly-Asp peptides-conjugated gold nanorods that target αvβ3 in melanoma cancer cells. J Nanobiotechnol. 2015;13(1):52.

    Article  CAS  Google Scholar 

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Correspondence to H. Ghaznavi or S. M. A. Hosseini Nami.

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Mirrahimi, M., Hosseini, V., Shakeri-Zadeh, A. et al. Modulation of cancer cells’ radiation response in the presence of folate conjugated Au@Fe2O3 nanocomplex as a targeted radiosensitizer. Clin Transl Oncol 21, 479–488 (2019). https://doi.org/10.1007/s12094-018-1947-8

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  • DOI: https://doi.org/10.1007/s12094-018-1947-8

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