Altın Nanopartiküller ile Dekore Edilmiş Metal Organik Çerçeve/Lipit Hibrit Yapılarının Hazırlanması ve Karakterizasyonu

Abstract

Drug delivery systems (DDS) are being used to transport active pharmaceutical molecules to the target area in the body to safely achieve the desired therapeutic effect. In recent years, one of the issues emphasized in the design of drug delivery systems is the creation of hybrid structures that enable combined therapies. By combining treatments such as chemotherapy and photothermal therapy, a controlled and targeted drug release is achieved, and a synergistic effect is created by minimizing the dose of the chemical to be taken into the body with the functionalized structure. One of the most important features to consider when choosing DDS is the porous structure of the carrier systems. In the category of porous materials, metal organic frameworks (MOFs) are one of the important structures used in many areas of materials science and chemical engineering. In this study, β-cyclodextrin-MOF (CD-MOF) structure with high surface area and porosity was synthesized by solvothermal/sonication/vapor diffusion method by selecting potassium as the non-toxic metal ion and β-cyclodextrin as the biocompatible organic ligand. Characterization of CD-MOFs was carried out by optical microscopy, XRD, SEM, AFM and FTIR. The outer surface of CDs has a hydrophilic structure, while the cavity is hydrophobic. As a result, hydrophobic molecules can enter the pores of the resulting CD-MOFs. However, due to the dissolution of the CD-MOF structure in water, the system's stability is quite low. For this reason, the surface of CD-MOFs was coated with 1H,1H,2H,2H-Perfluoro-1-decanol and its stability in water could be increased. Thus, the water resistance of CD-MOFs, which are the basic part of the drug carrier system, was increased and a suitable basis was prepared for the processes to be carried out from now on. Curcumin and orange OT molecules, which have different molecular structures and water solubility, were selected to be loaded into the cavity of CD-MOFs. Encapsulation of model molecules into CD-MOFs was achieved by two different methods: during synthesis and after synthesis. Since the encapsulation of model molecules can be achieved at higher rates during synthesis, this method was carried out and the release performance of the model molecules was examined. Considering the studies carried out in recent years, MOFs can be easily integrated into the structure of biomolecules such as lipid-based carrier systems and can incorporate the advantages of both systems. Within the scope of the thesis study, the surface of fluorocarbon-coated CD-MOFs (FTOH@CD-MOF) was covered with a lipid bilayer. Lipit@FTOH@CD-MOF with its lipid composite structure, it is aimed to ensure colloidal stability and increase cellular interaction. Then, the Lipit@FTOH@CD-MOF surface is coated with gold nanoparticles, which are photothermal therapy agents, to provide a combination theraphy. This process is carried out on the surface of the particles. In order to examine the advantage of the lipid coating in the outermost layer and its effect on photothermal therapy, the FTOH@CD-MOF structure was first coated with gold and then with lipid. This is Au@Lipit@FTOH@CD-MOF and Lipit@Au@ After obtaining the FTOH@CD-MOF structures, their photothermal effects were examined with a laser with a wavelength of 808 nm. The temperature of both particles was measured with a thermal camera under the laser and it was seen that the temperature increase could be achieved. In the Lipid@Au@FTOH@CD-MOF structure ,the presence of gold coating prevented the gold particles from falling off the surface and enabled higher temperatures to be reached with the same power and the same amount of gold. Characterization of Au@Lipit@FTOH@CD-MOF and Lipit@Au@FTOH@CD-MOF structures was carried out by optical microscope, fluorescence microscope, zeta potential, SEM-EDX and AFM. Finally, the functionality of Au@Lipit@FTOH@CD-MOF structures in different application areas can be demonstrated and their peroxidase-like enzyme effect has been demonstrated. As a result, multifunctional structures have been obtained with the ability to carry out chemotherapy and photothermal therapy in a single drug delivery system using Au@Lipid@FTOH@CD-MOF and Lipid@Au@FTOH@CD-MOF. This allows for the high loading of drug active substances with different physicochemical properties into the structure and enables controlled release. Additionally, these structures exhibit enzyme-like effects, making them suitable for various applications.