Investigation of the synthesis, characterization and anti-cancer effects of polyphenol doped ZIF-8 metal organic framework drug delivery systems

Cancer is a complex disease caused by uncontrolled cell division and proliferation and caused by genetic and environmental factors. The fact that very standard approaches have been developed for the treatment of different types of cancer has not changed the fact that cancer is a personal disease. Although progress has been made in the diagnosis and treatment of breast cancer, which is one of the most important factors threatening women's health, alternative methods are still needed to reduce side effects. Drug carrier systems developed with nanotechnology are good alternatives that meet this need. Metal organic framework (MOF) have shown fascinating possibilities in biomedical applications, designing a multifunctional drug delivery system based on MOF is highly important for cancer therapy. In this thesis, two drug delivery systems based on ZIF-8 were developed. In the first of these systems, 5-sulfosalicylic acid and BAs were loaded onto the BSA-centered ZIF-8 nanostructure. The capsule structure is provided by the ZIF layer for the storage of 5-sulfosalicylic acid and BAs under physiological conditions. The characterization results confirmed the syntheses. The pH dependent dissociation of ZIF-8 is an important parameter for pH sensitive drug release detection of 5-sulfosalicylic acid. 5-sulfosalicylic acid is not free at physiological pH, but is released from 5-sulfosalicylic acid/BSA@ZIF-8 and 5-sulfosalicylic acid/BSA/BAs@ZIF-8 nanostructures at acidic pH (5). The best biocompatibility has been found in 5-sulfosalicylic acid/BSA/BAs@ZIF-8 compared to the other synthesized nanosystems. In addition, 5-sulfosalicylic acid/BSA/BAs@ZIF-8 caused higher cytotoxicity in the MCF-7 cells compared to other nanosystems. As a result, it was concluded that the synthesized ZIF-8-based nanocarrier could provide therapeutic effects on breast cancer cells. As the second drug delivery system, a modified Fe-doped ZIF-8 MOF structure, which was modified with the phenolic compound gallic acid, was synthesized. It was aimed to increase the therapeutic efficiency of the developed drug delivery system with glucose oxidase enzyme and gold nanoparticles. The successful fabrication and structural properties of nanocarriers were verified using different characterization methods such as SEM, TEM, FT-IR, Zeta potential, XRD and TGA analyses. Studies on drug loading capacity and encapsulation efficiency have shown that the designed ZIF-8-based nano drug carrier structures have high encapsulation efficiency. pH-dependent drug releases were observed in in vitro drug release studies with ZIF-8@GA@Fe@5-FU, ZIF-8@GA@Fe@5-FU@GOx ve ZIF-8@GA@Fe@5-FU@Au systems at pH 5,0 and pH 7,4. According to in vitro cytotoxicity results, ZIF-8@GA@Fe@5-FU@GOx was determined as the most effective structure causing apoptosis and various morphological changes on MDA-MB-231 breast cancer cell lines. In addition, ZIF-8@GA@Fe@5-FU@Au structure containing gallic acid together with ZIF-8@GA@Fe@5-FU also showed luminescence properties. The obtained results show that the developed drug delivery systems are alternative and suitable representatives for drug delivery applications in breast cancer cell lines.