Design,synthesis and bio-applications of metal organic frameworks for drug delivery systems

One of the main limitations of chemotherapy today is the systemic toxicity and low bioavailability caused by the spread of drugs to non-target tissues. In this thesis, metal-organic frameworks (MOFs), which offer the potential for controlled release and targeted delivery, were evaluated as drug delivery systems. Within the scope of the study, ZIF-8 and Sr-TFA (strontium-terephthalic acid based MOF) structures were synthesized and loading studies were carried out with therapeutic agents such as Thymoquinone (TQ), Methotrexate (MTX), Curcumin (Kur) and 5-Fluorouracil (5-Fu). In ZIF-8 structures, multidrug loading strategies were developed by optimizing parameters such as metal:ligand ratio, solvent, surfactant and active ingredient. Sr-TFA structures were synthesized by flow-assisted solvothermal method and loaded with MTX. The structures were characterized by XRD, FTIR, SEM, TEM, TGA, DSC and DLS analyses; drug release was evaluated at different pH conditions and interpreted by kinetic models. Biological activity studies were performed on Caco-2, U-87MG, HeLa and MCF-7/TAM1 cells in 2D and 3D cultures; MTX@Sr-TFA-A structure showed high cytotoxic effect and apoptosis response especially in U-87MG and HeLa cells. The findings suggest that MOF-based systems have a strong potential in cancer therapy as multifunctional and selective drug delivery platforms.