Green Synthesis of ZnO Nanoparticles using Syzygium aromaticum (Clove) Extract and its Radio-Modifying Effect in Ehrlich Tumor-Bearing Mice

Radioresistance is a major obstacle that hinders cancer treatment. Identification of agents that can modify malignant cells’ response to radiation is a promising strategy to overcome this problem. We herein aimed to evaluate the potential radio-modifying effect of greenly synthesized Zinc oxide nanoparticles (ZnO NPs) in sensitizing Ehrlich tumor bearing mice to ionizing radiation. Syzygium aromaticum (Clove) extract was used as a reducing agent for the green and sustainable synthesis of ZnO NPs. Characterization of ZnO NPs was done using transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and zeta potential measurement. Ehrlich-bearing mice were treated with 6 Gy IR either alone or in combination with 5 mg/100 g BW ZnO NPs. Treatment response was assessed by monitoring tumor size, evaluation of apoptosis and oxidative stress markers, in addition to histopathological examinations. Our results indicated that the average size of synthesized ZnO NPs was 13.35±3.36 nm and XRD confirmed the hexagonal ZnO wurtzite structure. UV-Vis spectra revealed a strong absorption peak at 348 nm which is characteristic of ZnO. Treatment with sublethal dose of ZnO NPs resulted in a significant reduction in tumor size accompanied by a significant increase in BAX/BCL2 gene expression ratio, upregulation of TXNIP relative gene expression and decreased total antioxidant capacity in tumor tissues of mice treated with ZnO NPs prior to irradiation compared to those of mice treated with radiation alone with almost no detectable hepatic or renal toxicity. This significant influence of ZnO NPs on sensitizing tumors to ionizing radiation through induction of apoptosis and increasing oxidative stress in tumor cells suggested that ZnO NPs can be a promising, biocompatible agent for future applications.