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 degrees C compared to 25 degrees 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 mu g/ml), whereas UIO-66-Cur showed cytotoxicity toward MCF10A at high concentrations (78% viability at concentration of 200 mu g/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 can-cer cell lines.