Synthesis and characterization of magnetic nanoparticles loaded with curcumin and piperine and investigating the effects of these nanoparticles on Mir16-1 and mediators of apoptosis pathway in breast cancer

Curcumin (CUR) and piperine (PIP), as natural polyphenols, exhibit potent anti-cancer effects against many cancers, such as breast cancer. To enhance the efficiency of these drugs when used together and to impart magnetic properties to targeted drug delivery, CUR and PIP were loaded on magnetic iron nanoparticles (NPs) coated with silica (Fe 3 O 4 @SiO 2 ). CUR-loaded Fe 3 O 4 @SiO 2 NPs, PIP-loaded Fe 3 O 4 @SiO 2 NPs, and CUR/PIP-loaded Fe 3 O 4 @SiO 2 NPs were prepared using a co-participation approach followed by drug functionalization. The analysis of obtained NPs was done by Vibrating-Sample Magnetometer (VSM), Field Emission-Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Spectroscopy (EDS), Element Mapping, Fourier Transform Infrared Spectrometer (FT-IR), and X-ray Powder Diffraction (XRD). Analysis confirmed successful loading of drugs on Fe 3 O 4 @SiO 2 NPs and the presence of good magnetic properties of prepared NPs. According to the MTT assay, all drug-loaded NPs exhibited an anticancer effect on MCF-7 cells; however, the effect of Fe 3 O 4 @SiO 2 -CUR/PIP magnetic NPs was more pronounced than Fe 3 O 4 @SiO 2 -CUR and Fe 3 O 4 @SiO 2 -PIP applied alone, thus confirming the synergistic effect of the two drugs on NPs. Also, Flow Cytometry results showed the amount of cell apoptosis caused by the IC 50 concentration and 48-hour treatment with Fe 3 O 4 @SiO 2 -CUR, Fe 3 O 4 @SiO 2 -PIP, and Fe 3 O 4 @SiO 2 -CUR/PIP were estimated to be 63.25%, 61.1%, 75.5% respectively. Furthermore, the Real-time PCR results confirmed the synergistic effect of Fe 3 O 4 @SiO 2 -CUR/PIP nanoparticles in the ratio of Fe 3 O4@SiO 2 -CUR and Fe 3 O 4 @SiO 2 -PIP in apoptosis induction.These findings offer a novel perspective for targeted cancer therapy using CUR and PIP.