Efficient synergistic combination effect of Quercetin with Curcumin on breast cancer cell apoptosis through their loading into Apo ferritin cavity

Abstract Combination of natural agents has received a great attention in cancer treatment because of synergistically increased apoptotic effect on cancer cell lines by triggering several apoptotic signaling pathways. However, the hydrophobic nature, poor bioavailability and low cellular uptake of most natural agents limit their therapeutic effectiveness. The purpose of this study was to design Apoferritin nanoparticles loaded with Quercetin and Curcumin (Que-Cur-HoS-Apo NPs) and to test their synergistic antitumor properties on a breast cancer cell line (MCF7). The physico-chemical characterization of the Que-Cur-HoS-Apo NPs by Size Exclusion Chromatography (FPLC) and Dynamic Light Scattering (DLS) confirmed the encapsulation of the compounds in the protein cage with narrow size distribution in the range 17.4 ± 1.2 nm. Cell viability study indicated that Que-Cur-HoS-Apo NPs were able to exert a more pronounced effect at lower dose on the MCF7 cell line when compared to the free combination of the drugs. The Que-Cur-HoS-Apo system allowed cellular uptake of natural agents thus triggering enhanced apoptosis. These effects were confirmed by Annexin-V/7-AAD Staining Assay and intracellular Reactive Oxygen Species (ROS) quantitative detection. These results suggest the potential of Que-Cur-HoS-Apo NPs as a promising anti-cancer agent in breast cancer therapy and pave the way to examine Que-Cur-HoS-Apo NPs effect in vivo.