Breast Cancer Targeting of a Drug Delivery System through Postsynthetic Modification of Curcumin@N3-bio-MOF-100 via Click Chemistry.

Metal-organic frameworks (MOFs) offer many opportunities for applications across biology and medicine. Their wide range of chemical composition makes toxicologically acceptable formulation possible, and their high level of functionality enables possible applications as delivery systems for therapeutics agents. Surface modifications have been used in drug delivery systems to minimize their interaction with the bulk, improving their specificity as targeted carriers. Herein, we discuss a strategy to achieve a tumor-targeting drug-loaded MOF using "click" chemistry to anchor functional folic acid (FA) molecules on the surface of N3-bio-MOF-100. Using curcumin (CCM) as an anticancer drug, we observed drug loading encapsulation efficiencies (DLEs) of 24.02 and 25.64% after soaking N3-bio-MOF-100 in CCM solutions for 1 day and 3 days, respectively. The success of postsynthetic modification of FA was confirmed by 1H NMR spectroscopy, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography-mass spectrometry (LC-MS). The stimuli-responsive drug release studies demonstrated an increase of CCM released under acidic microenvironments. Moreover, the cell viability assay was performed on the 4T1 (breast cancer) cell line in the presence of CCM@N3-bio-MOF-100 and CCM@N3-bio-MOF-100/FA carriers to confirm its biological compatibility. In addition, a cellular uptake study was conducted to evaluate the targeting of tumor cells.

Establishment and characterization of an in vitro 3D ovarian cancer model for drug screening assays.

The acquired drug chemoresistance represents the main challenge of the ovarian cancer treatment. In addition, the absence of an adequate in vitro model able to reproduce the native tumor environment can contribute to the poor success rate of pre-clinical studies of new compounds. Three-dimensional (3D) culture models have been recently used for drug screening purposes due to their ability to reproduce the main characteristics of in vivo solid tumors. Here we describe the establishment and characterization of 3D ovarian cancer spheroids using different adenocarcinoma tumor cell lines (SKOV-3 and OVCAR-3 cells) in two different 3D scaffold-free methods: forced-floating in ultra-low attachment (ULA) plates and hanging drop (HD). Spheroids were evaluated in both 3D cultures in order to establish the best condition to perform the drug response analysis with Paclitaxel, a common drug used to treat ovarian cancer. SKOV-3 and OVCAR-3 spheroids with the desired characteristics (roundness close to 1.0 and diameter in the 200-500 µm range) were obtained using both methods after addition of the methylcellulose (MC) in the culture medium (0.25% and 0.5%, w/v). We also observed the presence of microvilli on the surface of the spheroids, higher presence of apoptotic cells and higher drug resistance, when compared with 2D cultures. The 3D cultures obtained seem to provide more reliable results in terms of drug response than those provided by 2D monolayer culture. The forced floating method was considered more suitable and straightforward to generate ovarian cancer spheroids for drug screening/cytotoxicity assays.