Fabrication of degradable polymer coated nanoparticles

Abstract

In recent years, interest in polymer drug conjugate delivery systems has increased. When these polymer drug conjugate systems are conjugated with magnetic nanoparticles, they can be used as delivery systems by creating magnetic field. In this thesis, firstly monodisperse oleic acid coated, iron oxide nanoparticles were synthesized by thermal decomposition method. By place exchange reaction, these nanoparticles were coated by chain transfer agents which are modified with dopamine and have disulfide bond in their structure. Then PEG based polymer were grafted from the surface of iron oxide nanoparticles by RAFT polymerization in order to make them hydrophilic. In this system, there are disulfide bonds between polymeric brushes and nanoparticles and these bonds can be cleaved by glutathione which is found in excess at diseased tissues. Importantly, it is difficult to characterize the molecular weights of the polymers which were grown from the surface of nanoparticles ‘by grafting-from’ approach. We envisioned that mild methods to cleave the polymers from nanoparticle surfaces will facilitate their characterization. We demonstrate that treatment with glutathione cleaves the polymeric brushes from nanoparticles under mild conditions. Thus, this study provides an excellent way to analyze molecular weight and molecular weight distributions of polymer brushes. In order to understand the cleavage kinetics, polymer brushes containing fluorescent dye were synthesized. Also, the fluorescent dye acts as a model hydrophobic drug. Incorporation of the dye into polymer brushes provides it with water solubility. Finally, we demonstrated that the trithiocarbonate end groups of polymers can be modified with azo initiators for purposes of attachment of any biomolecules.