Synthesis and characterization of actively HER-2 Targeted Fe₃O₄@Au nanoparticles for molecular radiosensitization of breast cancer

Abstract

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.

Keywords: Breast cancer, Radiation therapy, Active targeting, Trastuzumab, Au nanoparticles