Interaction of Poly(vinyl alcohol) and chitosan coated iron oxide nanoparticles with cell membrane models

Nanotechnology is being used at different fields from energy to food industry but its application to medical field, such as tissue engineering, bioimaging, drug design, diagnosis, is more recent. According to the World Health Organization (WHO), 8.8 million people were reported dead because of the cancer in 2015. Cancer can be treated with chemotherapy, radiotherapy and surgery but these treatment methods have serious side effects since cancer drugs are not selective so they affect both healthy and cancerous cells. One of the approaches to reduce the toxic side effects and improve patient life quality is the implementation of nanotechnology to the development of new drugs and therapies. Magnetic nanoparticles are usually made up of nickel, cobalt and iron. Because of their magnetic properties, they can be transferred to desired location with the help of external magnetic field. Generally, magnetite, hematite, maghemite and goethite are known as iron oxides types. Iron oxide nanoparticles (IOPs) are commonly preferred as MRI agent, and targeted drug design. They are, however, toxic and cause problem in physiological environment because of their negative surface charge, easy agglomeration, low stability, and free radical formation. Therefore, they should be modified to reduce their toxicity and coating their surface with polymers is an effective method proposed by different groups. In this study, iron oxide nanoparticles were coated with two different polymers and the interaction of these particles with cells were studied using artificial cell membrane models. For this purpose, chitosan and poly(vinyl alcohol) (PVA) were selected because of their biodegradable and biocompatible characteristics. Polymers were coated on IOPs surfaces by adsorption method because of its high efficiency and simplicity. In this method, polymer solutions at different concentrations were mixed with IOPs. Optimal polymer concentration was determined according to colloidal stability. Characterizations of the IOPs were done using different techniques. Zeta potential was measured to determine the surface charges, and stability, rheology to observe flow behavior, Dynamic Light Scattering (DLS) to measure particle size, and Fourier Transform Infrared Spectroscopy (FTIR) to investigate binding between IOPs and polymers. After the characterization, interaction between cell and coated and uncoated IOPs were investigated with liposome, a simple biomimetic cell membrane model. Quartz Crystal Microbalance with Dissipation (QCM-D) is used to investigate these interactions in real time and label-free. QCM-D uses piezoelectric effect of quartz crystal. When voltage is applied, quartz crystal oscillates with a defined frequency and this frequency is sensitive to the amount of material attached to the surface. Adsorption/desorption or solid/liquid interaction can be observed according to the frequency shift (Δf). QCM-D also measures viscoelastic properties of adsorbed particles on surface with changes of dissipation (ΔD) at the same time. In this thesis, the interaction of PVA and chitosan fully coated, partially coated, and uncoated IOPs were investigated with neutral, positive and negatively charged liposome layers. By using QCM-D, interactions of particles with cell were estimated in a shorter time and cheaper than cell culture experiments. Results show that, coating properties, structure and charge of lipids affect the interactions between them and electrostatic interactions are significant parameter. In the future studies, chemotherapeutic drug loaded particles can be studied both in QCM-D and cell culture to see their effect to the cells.