A Promising, Novel Radiosensitizer Nanodrug Complex for Oral Cavity Cancer: Cetuximab and Cisplatin-Conjugated Gold Nanoparticles

A Promising, Novel Radiosensitizer Nanodrug Complex for Oral Cavity Cancer: Cetuximab and Cisplatin-Conjugated Gold Nanoparticles

Background: Nanomedicine has provided promising tools for the imaging, diagnosis, and treatment of cancer. Gold nanoparticles (GNPs) may be useful in enhancing the efficacy of radiotherapy, such as radiosensitization, in cancer therapy. Aims: To develop a nanodrug complex containing cetuximab (C225, CTX) and cisplatin (CDDP) conjugated with GNPs and to investigate its cytotoxic effects on oral cavity cancer cells when combined with radiotherapy. Study Design: In vitro cell culture study. Methods: The GNPs were synthesized and successfully conjugated with cetuximab and cisplatin. Cell viability was monitored by the xCELLigence real-time cell analysis (RTCA) single-plate (SP) system in GNP-treated UPCI-SCC-131 cells for 48 hours. Cells with/without GNPs were irradiated with 6 MV X-rays, and colony formation was assayed to investigate the long-term effects of GNPs and the nanodrug complex after irradiation on radiotherapy-resistant oral cavity cancer cells. Results: The GNPs entered the tumor cells, and GNP–CDDP (P < .0001) and GNP–CDDP–CTX (P < .0001) were shown to cause a decrease in cell viability. GNP and GNP–CTX combined with radiotherapy led to greater reduction on UPCI-SCC-131 colony numbers, than radiation alone (P = .0369) and radiation with free CTX, with sensitizing enhancement ratios of 1 : 2 and 1 : 9, respectively. Conclusion: The cetuximab and cisplatin-conjugated gold nanodrug complex has a great potential to increase cytotoxicity and overcome resistance to radiotherapy, in the treatment of oral cavity cancer.

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  • 1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137-2150. [CrossRef]
  • 2. Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83(4):489-501. [CrossRef]
  • 3. Kim CK, Ghosh P, Rotello VM. Multimodal drug delivery using gold nanoparticles. Nanoscale. 2009;1(1):61-67. [CrossRef]
  • 4. McQuaid HN, Muir MF, Taggart LE, et al. Imaging and radiation effects of gold nanoparticles in tumour cells. Sci Rep. 2016;6:19442. [CrossRef]
  • 5. Butterworth KT, McMahon SJ, Currell FJ, Prise KM. Physical basis and biological mechanisms of gold nanoparticle radiosensitization. Nanoscale. 2012;4(16):4830- 4838 [CrossRef].
  • 6. Zhang X. Gold nanoparticles: recent advances in the biomedical applications. Cell Biochem Biophys. 2015;72(3):771-775. [CrossRef]
  • 7. Zhang X, Xing JZ, Chen J, et al. Enhanced radiation sensitivity in prostate cancer by gold-nanoparticles. Clin Invest Med. 2008;31(3):E160-E167. [CrossRef]
  • 8. Jeremic B, Aguerri AR, Filipovic N. Radiosensitization by gold nanoparticles. Clin Transl Oncol. 2013;15(8):593-601. [CrossRef]
  • 9. Pottier A, Borghi E, Levy L. New use of metals as nanosized radioenhancers. Anticancer Res. 2014;34(1):443-453.
  • 10. O-charoenrat P, Rhys-Evans PH, Archer DJ, Eccles SA. C-erbB receptors in squamous cell carcinomas of the head and neck: clinical significance and correlation with matrix metalloproteinases and vascular endothelial growth factors. Oral Oncol. 2002;38(1):73-80. [CrossRef]
  • 11. Sarkis SA, Abdullah BH, Abdul Majeed BA, Talabani NG. Immunohistochemical expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma in relation to proliferation, apoptosis, angiogenesis and lymphangiogenesis. Head Neck Oncol. 2010;2:13. [CrossRef]
  • 12. Ryott M, Wangsa D, Heselmeyer-Haddad K, et al. EGFR protein overexpression and gene copy number increases in oral tongue squamous cell carcinoma. Eur J Cancer. 2009;45(9):1700-1708. [CrossRef]
  • 13. Ang KK, Berkey BA, Tu X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62(24):7350-7356.
  • 14. Galizia G, Lieto E, De Vita F, et al. Cetuximab, a chimeric human mouse antiepidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer. Oncogene. 2007;26(25):3654-3660. [CrossRef]
  • 15. Li S, Schmitz KR, Jeffrey PD, et al. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell. 2005;7(4):301-311. [CrossRef]
  • 16. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamouscell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567-578. [CrossRef]
  • 17. Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23(34):8646-8654. [CrossRef]
  • 18. Zhang XD, Wu D, Shen X, et al. Size-dependent radiosensitization of PEG-coated gold nanoparticles for cancer radiation therapy. Biomaterials. 2012;33(27):6408- 6419. [CrossRef]
  • 19. Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc. 2006;1(5):2315-2319. [CrossRef]
  • 20. Ma N, Wu FG, Zhang X, et al. Shape-dependent radiosensitization effect of gold nanostructures in cancer radiotherapy: comparison of gold nanoparticles, nanospikes, and nanorods. ACS Appl Mater Interfaces. 2017;9(15):13037-13048. [CrossRef]
  • 21. Pullambhatla M, Rowe SP, Lisok A, et al. Enhancement of radiotherapy with human mesenchymal stem cells containing gold nanoparticles. Tomography. 2020;6(4):373- 378. [CrossRef]
  • 22. Nair S, Trummell HQ, Rajbhandari R, et al. Novel EGFR ectodomain mutations associated with ligand-independent activation and cetuximab resistance in head and neck cancer. PLoS One. 2020;15(2):e0229077. [CrossRef]
  • 23. Eskiizmir G, Çalıbaşı G, Uysal T, Ellidokuz H, Baskın Y. Cetuximab alone has a dose-dependent antitumor effect in oral cavity cancer cells: an in vitro study. ENT Update. 2016;6(3):105-109. [CrossRef]
  • 24. Pan Y, Neuss S, Leifert A, et al. Size-dependent cytotoxicity of gold nanoparticles. Small. 2007;3(11):1941-1949. [CrossRef]
  • 25. Pan Y, Leifert A, Ruau D, et al. Gold Nano- particles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. Small. 2009;5(18):2067- 2076. [CrossRef]
  • 26. Leve F, Bonfim DP, Fontes G, Morgado-Díaz JA. Gold nanoparticles regulate tight junctions and improve cetuximab effect in colon cancer cells. Nanomedicine. 2019;14(12):1565-1578. [CrossRef]
  • 27. Davidi ES, Dreifuss T, Motiei M, et al. Cisplatin-conjugated gold nanoparticles as a theranostic agent for head and neck cancer. Head Neck. 2018;40(1):70-78. [CrossRef]
  • 28. Vechia ICD, Steiner BT, Freitas ML, et al. Comparative cytotoxic effect of citratecapped gold nanoparticles with different sizes on noncancerous and cancerous cell lines. J Nanopart Res. 2020;22(6):133. [CrossRef]
  • 29. Chueh PJ, Liang RY, Lee YH, Zeng ZM, Chuang SM. Differential cytotoxic effects of gold nanoparticles in different mammalian cell lines. J Hazard Mater. 2014;264:303-312. [CrossRef]
  • 30. Aryal S, Grailer JJ, Pilla S, Steeber DA, Gong S. Doxorubicin conjugated gold nanoparticles as water-soluble and pH-responsive anticancer drug nanocarriers. J Mater Chem. 2009;19(42):7879. [CrossRef]
  • 31. Sankunny M, Parikh RA, Lewis DW, et al. Targeted inhibition of ATR or CHEK1 reverses radioresistance in oral squamous cell carcinoma cells with distal chromosome arm 11q loss. Genes Chromosomes Cancer. 2014;53(2):129-143. [CrossRef]
  • 32. Popovtzer A, Mizrachi A, Motiei M, et al. Actively targeted gold nanoparticles as novel radiosensitizer agents: an in vivo head and neck cancer model. Nanoscale. 2016;8(5):2678-2685. [CrossRef]
  • 33. Ma N, Jiang YW, Zhang X, et al. Enhanced radiosensitization of gold nanospikes via hyperthermia in combined cancer radiation and photothermal therapy. ACS Appl Mater Interfaces. 2016;8(42):28480-28494. [CrossRef]
  • 34. Ma N, Liu P, He N, et al. Action of gold nanospikes-based nanoradiosensitizers: cellular internalization, radiotherapy, and autophagy. ACS Appl Mater Interfaces. 2017;9(37):31526-31542. [CrossRef]
  • 35. Zhang X, Chen X, Jiang YW, et al. Glutathione-depleting gold nanoclusters for enhanced cancer radiotherapy through synergistic external and internal regulations. ACS Appl Mater Interfaces. 2018;10(13):10601-10606. [CrossRef]
Balkan Medical Journal-Cover
  • ISSN: 2146-3123
  • Başlangıç: 2015
  • Yayıncı: Erkan Mor
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