Çok fonksiyonlu manyetik nanoparçacıkların hedef kanser tedavisinde kullanılabilmesi için hazırlanması, karakterizasyonu ve in vitro çalışmaları

According to World Health Organization's statistics, it is expected that annual cancer cases will rise from 14 million in 2012 to 22 within the next 2 decades. Most common clinically used cancer treatments are surgery, chemotherapy, radiation therapy etc. However, these treatment options can be invasive and have many side effects. The major disadvantage of most chemotherapeutic approaches for cancer treatment is that they are non-specific for tumor tissue, hence toxicity to healthy cells and manifestation of side effects. To overcome these disadvantages, a new approach of using multifunctional magnetic nanoparticles (MNP) can eliminate the disadvanteges of traditional treatments. Popularly researched MNPs are iron oxides such as magnetite, maghemite, hematite and geothite for designing a multifunctional magnetic nanoparticle that can deliver drug to the target site. Recently, iron oxide nanoparticles (IONPs) have shown great potential in therapeutic and diagnostic applications, such as imaging, magnetic hyperthermia treatments and drug delivery systems. IONPs, biocompatibility in moderate doses, easy of surface modification, known metabolic pathways, variety of their sizes and their magnetic properties allow them to be suitable for therapeutic applications. These properties and their ability to be manipulated upon application of a magnetic field allow them to be utilized as therapeutic and diagnostic tools. Iron oxide nanoparticles have been widely used in preclinical experiments for imaging, magnetic hyperthermia and drug delivery. Besides the advantages mentioned above, IONPs also might cause cytotoxicity and can form free radicals in the system. For this reason, these particles must be modified to reduce these effects. One of the most sensitive parameters in toxicity is the surface coating of the nanoparticles. To induce lower toxicity, nanoparticles can be coated with biocompatible coating, which is an easier, cheaper method comparing to synthetic polymers. Also loading anti tumor drugs to MNPs surface is challenging without the help of an polymer.so using biocompatible biopolymers for the functionalization of nanoparticles by modulating physical and chemical properties (surface charge, etc.) improving stability, reducing toxicity and protection of drugs and nanoparticles may eliminate existing disadvantages. Also evaluating the toxicological effects of MNPs both in vitro and in vivo is crucial for the development of MNPs. Therefore, this research reports the synthesis, characterization, and in vitro evaluations of multifunctional magnetic iron oxide nanoparticles coated with biopolymers. This reported nanodrug system could potentially open up new possibilities in the design of therapeutic agents using multifunctional nanoparticles. When designing and synthesizing multifunctional nanoparticles all advantages and disadvantades previously mentioned must be considered. To reach a positive result characterization, optimum polymer concentration determination is important. Optimum concentration of the biopolymers can be determined by characterization of the colloidal properties of the MNP particles. The desired MNP-biopolymer structure suitable for targeted drug delivery must have fully covered surfaces by the biopolymers and stabile structures. The flocculation properties of MNPs can be determied by their rheological measurements and the surface properties can be determied by their electrokinetical measurements. The hydrodynamic radius of the MNPs can be controlled by the light scattering experiments. Characterization provides an opportunity to analyze the results of experiments and to choose the next step to achieve expected results. Characterization techniques are required to determine magnetic nanoparticle properties such as size, crystal structure, material's thermal stability, absorbtion spectrum and magnetic behavior. Characterization of nanostructured materials is important because human eye cannot determine such small structures and their properties. The stabile and fully covered surfaces of the MNPs were characterized by the conventional methods such as scanning electron microscope (SEM) for the determination of the size and morphology, X-ray diffraction (XRD) to determine crystal structure, Fourier transform infrared spectroscopy (FTIR) to analyze the chemical bonds and functional groups, thermogravimetric analysis (TGA) to determine material's thermal stability and vibrating sample magnetometers (VSM) to measure the magnetic properties.After the characterization of MNP, the in vitro evaluations will give insight about biological compatibility and toxicity of synthesized particles. The only possibility of the targeted drug delivery of magnetic particles is to apply external magnetic field. However, when an external magnetic field is applied there is a drastic change on the flow properties of the magnetic suspensions. The magnetorheological effect of the drug delivery MNPs are rarely researched in the literature and very important considering the applications. In this study we examined MNPs magnetorheological properties. The main purposes this project is to have stable and fully covered surfaces of Fe2O3 particles by coating with HEC and cellulosic polymers and to obtain non-toxic biocompatible multifunctional magnetic particles. When particles reach desired properties cancer drugs will be adsored on the particles and the effect of these particles on the cancer cells will be examined. To achieve the goals mentioned above Fe2O3 particles were treated with biopolymers in a variable range of polymer concentration. Particles with optimum polymer concentrations were characterized and tested for toxicity. The reported nanodrug system in this thesis showed that multifunctional nanoparticles synthesized could potentially open up new possibilities in the design of therapeutic agents using them. Future efforts could be to investigate the in vivo characteristics of these integrated nanostructures.