Synthesis and characterization of actively HER-2 Targeted Fe 3 O 4 @Au nanoparticles for molecular radiosensitization of breast cancer

Synthesis and characterization of actively HER-2 Targeted Fe 3 O 4 @Au nanoparticles for molecular radiosensitization of breast cancer Behnaz Babaye Abdollahi Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran http://orcid.org/0000-0003-3400-7051 Marjan Ghorbani Nutration Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Hamed Hamishehkar Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Reza Malekzadeh Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Alireza Farajollahi Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Imam Reza Educational Hospital, Radiotherapy Department, Tabriz University of Medical Sciences, Tabriz, Iran http://orcid.org/0000-0001-5549-9847

Introduction: The present study was done to assess the effect of molecularly-targeted core/shell of iron oxide/gold nanoparticles (Fe3O4@AuNPs) on tumor radiosensitization of SKBr-3 breast cancer cells. Methods: Human epidermal growth factor receptor-2 (HER-2)-targeted Fe3O4@AuNPs were synthesized by conjugating trastuzumab (TZ, Herceptin) to PEGylated (PEG)-Fe3O4@AuNPs (41.5 nm). First, the Fe3O4@Au core-shell NPs were decorated with PEG-SH to synthesize PEG-Fe3O4@AuNPs. Then, the TZ was reacted to OPSS-PEG-SVA to conjugate with the PEG-Fe3O4@AuNPs. As a result, structure, size and morphology of the developed NPs were assessed using Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy. The SKBr-3 cells were treated with different concentrations of TZ, Fe3O4@Au, and TZ-PEG-Fe3O4@AuNPs for irradiation at doses of 2, 4, and 8 Gy (from X-ray energy of 6 and 18 MV). Cytotoxicity was assessed by MTT assay, BrdU assay, and flow cytometry. Results: Results showed that the targeted TZ-PEG-Fe3O4@AuNPs significantly improved cell uptake. The cytotoxic effects of all the studied groups were increased in a higher concentration, radiation dose and energy-dependent manner. A combination of TZ, Fe3O4@Au, and TZ-PEG-Fe3O4@AuNPs with radiation reduced cell viability by 1.35 (P=0.021), 1.95 (P=0.024), and 1.15 (P=0.013) in comparison with 8 Gy dose of 18 MV radiation alone, respectively. These amounts were obtained as 1.27, 1.58, and 1.10 for 8 Gy dose of 6 MV irradiation, respectively. Conclusion: Radiosensitization of breast cancer to mega-voltage radiation therapy with TZ-PEG-Fe3O4@AuNPs was successfully obtained through an optimized therapeutic approach for molecular targeting of HER-2.
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