Preparation of UiO-66 loaded Letrozole nano-drug delivery system: enhanced anticancer and apoptosis activity

Abstract

AbstractThe use of drug delivery systems in targeting and achieving the targeting of drugs in treating diseases, especially cancer, has attracted the attention of researchers. Letrozole is one of the drugs for the treatment of breast cancer. In this study, the organic-metallic pharmaceutical porous nanostructure based on zirconium UiO-66 loaded letrozole was synthesized. Its cytotoxicity and effect on apoptosis and migration against breast cancer cell line were investigated. In this experimental study, the UiO-66 nanoparticle-loaded letrozole was synthesized using zirconium chloride (ZrCl4), dimethylformamide (DMF), and HCl. Its characteristics were determined by scanning electron microscopy, and its average size was determined by the DLS method. Also, the rate of letrozole drug release from the nanoparticle was investigated in 24, 48, and 72 h. In addition, its cytotoxicity effects were investigated using the MTT colorimetric method at concentrations of 3.125-100 µg/ml against the breast cancer cell line (MCF-7) in the periods of 48 and 72 h. Also, the expression level of apoptotic genes Bax and Bcl2 was investigated by the Real-Time PCR method. Also, the amount of cell migration was done by the migration assay method. The results showed that UiO-66 bound to letrozole had a spherical morphology and an average size of 9.2 ± 160.1. Also, the letrozole drug was loaded by 62.21 ± 1.80% in UiO-66 nanoparticles and had a slower release pattern than free letrozole in the drug release test, so within 72 h, 99.99% of free letrozole was released in If in UiO-66 containing letrozole, 57.55% of the drug has been released. Also, the cytotoxicity results showed that UiO-66 bound to letrozole has more significant cytotoxic effects than free letrozole (p < 0.05). Also, the results of Bax and Bcl2 gene expression showed that the treatment of MCF-7 cells with UiO-66 nanoparticles attached to letrozole increased the expression of Bax and Bcl2 genes compared to the reference gene Beta-actin in MCF-7 cell line, respectively. (p < 0.05) increased by 3.71 ± 0.42 and (p < 0.01) decreased by 0.636 ± 0.034 (p < 0.05). Cell migration results showed that the concentration of 50 µg/ml of UiO-66 bound to letrozole decreased the migration of MCF-7 cells. Generally, the results of this study showed that UiO-66 loaded letrozole can be used as a suitable drug carrier for cellular purposes, as it has increased the effects of cytotoxicity and the rate of apoptosis in breast cancer cell line (MCF-7), so it can be used with more studies used nanocarriers as a drug delivery system.