Synthesis and characterization of platinum decorated iron oxide nanoparticles for biomedical applications

Abstract

This dissertation focuses on the development of a bifunctional nanoparticle system that can potentially offer simultaneous imaging and therapy in the future. Recently, small platinum (Pt) nanoparticles (< 5 nm) have shown great potential in therapeutic applications, such as DNA dissociation, radiation therapy, and oxidative stress treatment. Therefore, the small Pt nanoparticles of size comparable to DNA grooves are chosen as potential therapeutic components in this research. However, such small sized Pt nanoparticles tends to aggregate, and are difficult to target. Therefore, this research reports the synthesis, characterization, and DNA interaction of small Pt decorated iron oxide nanoparticles. The iron oxide carriers provide stability to the small Pt nanoparticles, and can potentially serve as MRI contrast agents. The hypothesis of this research is that the Pt nanoparticles supported on iron oxide nanoparticle surfaces can effectively interact with DNA molecules similar to the free Pt nanoparticles. A reproducible synthetic technique was first developed to prepare iron oxide nanoparticles with excellent size control and narrow size distribution. Subsequently, two different approaches were utilized to produce multiple small Pt nanoparticle attached iron oxide nanoparticles. The first route involved attachment of Pt nanoparticles onto iron oxide seeds of various shapes in an organic solvent, followed by an aqueous phase transfer. Here, the shape of the nanoparticles was controlled to facilitate heterogeneous nucleation of Pt nanoparticles. The protective biocompatible polymer coating (polyacrylic acid) in this method could prevent interaction of the Pt nanoparticles with undesirable biomolecules. Several non-spherical iron oxide nanoparticles were explored, including whiskers, worms, plates, and flowers. In the second method, an aqueous phase ligand exchange process was performed first, prior to the deposition of multiple Pt nanoparticles. This facile method provided more accessibility of the Pt nanoparticles for DNA interactions. The DNA interaction of these nanoparticles was investigated using gel electrophoresis, electron microscopy, dynamic light scattering, and atomic absorption spectroscopy. By comparing with control DNA, we suggested that two possible interactions between DNA and Pt-iron oxide nanoparticles were present: (1) DNA molecules directly linked to the Pt-iron oxide nanoparticles, and (2) DNA molecules de-attached the Pt nanoparticles from the iron oxide support. This reported nanodrug system could potentially open up new possibilities in the design of therapeutic agents using multifunctional nanoparticles. Future efforts are to investigate the in vivo characteristics of this integrated nanostructure.