Anticancer effect of tamoxifen and Fe3O4@SiO2@Cu hybrid NPs on malignant human breast cancer cell (MCF-7)

Abstract

This work examined whether co-administration of tamoxifen (TAM) and Fe₃O₄@SiO₂@Cu hybrid NPs to MCF-7 cancer cells may have an impact in cell cytotoxicity by increasing IC₅₀ and apoptosis. NPs were produced using an electrochemical process and showed a negative surface charge (−35 ± 2 mV) and average hydrodynamic diameter and particle size of ca. 83 ± 1 nm and 60 ± 4 nm as derived from dynamic light scattering and electron microscopy images, respectively, and being colloidally stable in physiological conditions to long term. The particles were also shown to be non-toxic to cells in a wide range of concentrations. Notably, the co-administration of TAM (15 μg/mL) with Fe₃O₄@SiO₂@Cu nanocomposite (125 μg/mL) significantly reduced the IC₅₀ of TAM from 15.1 μg/mL to 7.8 μg/mL (P < 000.1) after 72 h of incubation. Moreover, alterations in p53, MDM2, and MDM4 gene expressions were determined using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) directly related to the cell-death apoptotic pathway. The expression level of p53 increased 2.1 times upon the co-administration of TAM with Fe₃O₄@SiO₂@Cu NPs nanoparticles compared with untreated MCF-7 cancer cells as the control group (P < 0.001); conversely, expression of MDM2 and MDM4 genes were 2.6 and 2.9 times lower compared to control cancerous cells (P < 0.001). On the other hand, fluorescence microscopy analysis showed that co-administration of TAM (15 µg/mL) with Fe₃O₄@SiO₂@Cu NPs (125 µg/mL) caused cell nuclei to break up. This was accompanied by changes in the cell shape, which proved that the nanoparticle-drug combination was highly cytostatic. Therefore, TAM co-administrated with Fe₃O₄@SiO₂@Cu NPs could be a promising and possible way to deliver TAM in breast cancer chemotherapy and enhanced its therapeutic effect.