The efficacy of current cancer therapies is limited due to several factors, including drug resistance and non-specific toxic effects. Due to their tuneable properties, silver nanoparticles (Ag NPs) and graphene derivative-based nanomaterials are now providing new hope to treat cancer with minimum side effects. Here, we report a simple, inexpensive, and eco-friendly protocol for the preparation of silver-reduced graphene oxide nanocomposites (Ag/RGO NCs) using orange peel extract. This work was planned to curtail the use of toxic chemicals, and improve the anticancer performance and cytocompatibility of Ag/RGO NCs. Aqueous extract of orange peels is abundant in phytochemicals that act as reducing and stabilizing agents for the green synthesis of Ag NPs and Ag/RGO NCs from silver nitrate and graphene oxide (GO). Moreover, the flavonoid present in orange peel is a potent anticancer agent. Green-prepared Ag NPs and Ag/RGO NCs were characterized by UV-visible spectrophotometry, transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and dynamic light scattering (DLS). The results of the anticancer study demonstrated that the killing potential of Ag/RGO NCs against human breast cancer (MCF7) and lung cancer (A549) cells was two-fold that of pure Ag NPs. Moreover, the cytocompatibility of Ag/RGO NCs in human normal breast epithelial (MCF10A) cells and normal lung fibroblasts (IMR90) was higher than that of pure Ag NPs. This mechanistic study indicated that Ag/RGO NCs induce toxicity in cancer cells through pro-oxidant reactive oxygen species generation and antioxidant glutathione depletion and provided a novel green synthesis of Ag/RGO NCs with highly effective anticancer performance and better cytocompatibility.
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