SnO2-Doped ZnO/Reduced Graphene Oxide Nanocomposites: Synthesis, Characterization, and Improved Anticancer Activity via Oxidative Stress Pathway

Abstract

Background: Therapeutic selectivity and drug resistance are critical issues in cancer therapy. Currently, zinc oxide nanoparticles (ZnO NPs) hold considerable promise to tackle this problem due to their tunable physicochemical properties. This work was designed to prepare SnO₂-doped ZnO NPs/reduced graphene oxide nanocomposites (SnO₂-ZnO/rGO NCs) with enhanced anticancer activity and better biocompatibility than those of pure ZnO NPs.

Materials and methods: Pure ZnO NPs, SnO₂-doped ZnO (SnO₂-ZnO) NPs, and SnO₂-ZnO/rGO NCs were prepared via a facile hydrothermal method. Prepared samples were characterized by field emission transmission electron microscopy (FETEM), energy dispersive spectroscopy (EDS), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), ultraviolet-visible (UV-VIS) spectrometer, and dynamic light scattering (DLS) techniques. Selectivity and anticancer activity of prepared samples were assessed in human breast cancer (MCF-7) and human normal breast epithelial (MCF10A) cells. Possible mechanisms of anticancer activity of prepared samples were explored through oxidative stress pathway.

Results: XRD spectra of SnO₂-ZnO/rGO NCs confirmed the formation of single-phase of hexagonal wurtzite ZnO. High resolution TEM and SEM mapping showed homogenous distribution of SnO₂ and rGO in ZnO NPs with high quality lattice fringes without any distortion. Band gap energy of SnO₂-ZnO/rGO NCs was lower compared to SnO₂-ZnO NPs and pure ZnO NPs. The SnO₂-ZnO/rGO NCs exhibited significantly higher anticancer activity against MCF-7 cancer cells than those of SnO₂-ZnO NPs and ZnO NPs. The SnO₂-ZnO/rGO NCs induced apoptotic response through the upregulation of caspase-3 gene and depletion of mitochondrial membrane potential. Mechanistic study indicated that SnO₂-ZnO/rGO NCs kill cancer cells through oxidative stress pathway. Moreover, biocompatibility of SnO₂-ZnO/rGO NCs was also higher against normal breast epithelial (MCF10A cells) in comparison to SnO₂-ZnO NPs and ZnO NPs.

Conclusion: SnO₂-ZnO/rGO NCs showed enhanced anticancer activity and better biocompatibility than SnO₂-ZnO NPs and pure ZnO NPs. This work suggested a new approach to improve the selectivity and anticancer activity of ZnO NPs. Studies on antitumor activity of SnO₂-ZnO/rGO NCs in animal models are further warranted.

Keywords: ZnO nanocomposites; better selectivity; breast cancer; caspase-3; improved anticancer activity; reactive oxygen species.