Engineered UIO-66 metal-organic framework for delivery of curcumin against breast cancer cells: An in vitro evaluation

Curcumin (Cur) is a traditional herb with known anticancer properties against various malignancies such as breast cancer. In this study, a metal-organic framework (MOF) based on UIO-66 with excellent water stability was prepared to deliver Cur into MDA-MB-231 and SKBR3 human breast cancer cell lines. The size of the fabricated UIO-66 ranged from 100 to 150 nm with a spherical shape and triangular base pyramid morphology. Favorable adsorption of Cur on the UIO-66 was approved by Fourier transform infrared spectroscopy (FTIR). The release profile exhibited a slow pH-dependent release of Cur from UIO-66 with significant enhancement in the acidic microenvironment (50, 55, and 70% Cur release from UIO-66-Cur in pH values of 7.4, 6.5, and 5.4 in 72 h test), showing UIO-66-Cur versatile releasing capacity in the acidic milieu of breast cancer. The characterization and structural elucidation of nanoparticles were evaluated by N2 adsorption–desorption, thermogravimetric analysis (TGA), differential thermogravimetric (DTG), Brunauer Emmett-Teller (BET), Barrett-Joyner Halenda (BJH), and adsorption kinetics that showed promising results. Particularly, the UIO-66-Cur exhibited the highest adsorption capacity for Cur. The kinetics of drug adsorption were investigated by three well-known kinetic models, and the result indicated that the adsorption of the drug into the synthesized MOFs followed the pseudo-second-order model. TGA and DTG curves of UIO-66 demonstrated a three-step weight reduction. The N2 adsorption/desorption isotherms and pore size distribution characteristics of UIO-66. The BET surface area and total pore volume of UIO-66 were computed to be 910.58 m2/g and 0.49 cm3/g. The size and entrapment efficacy (EE) of nanoparticles were more stable at 4 °C compared to 25 °C. Furthermore, the cytotoxic effects of UIO-66-Cur against MDA-MB-231 and SKBR3 cell lines were demonstrated using MTT assay, flow cytometry, gene expression profile, migration assay, and DAPI staining. The MTT assay revealed the high biocompatibility of UIO-66 with MCF10A healthy breast cell line (95% viability at a concentration of 200 μg/ml), whereas UIO-66-Cur showed cytotoxicity toward MCF10A at high concentrations (78% viability at concentration of 200 μg/ml). Furthermore, loading of Cur into UIO-66 notably increased its anticancer activity as the IC50 of UIO-66-Cur was significantly lower than Cur (72.2 vs. 159.3 against SKBR3 and 109.3 vs. 269.1 against MD-MBA-231 in 72 h test). It was shown that loading of Cur into UIO-66 profoundly promotes its anticancer activity as UIO-66-Cur significantly induced caspase 3 and caspase 9 and inhibited MMP-2, MMP-9 and cyclin E/D expression in cancer cell lines.