Superparamagnetic Iron oxide-Gold Core-Shell Nanoparticles for Biomedical Applications G. Saini * , D. Shenoy * , D.K. Nagesha * , R. Kautz ** , S. Sridhar * and M. Amiji * * The Nanomedicine Consortium, Northeastern University, Boston, MA 02115 ** Barnett Institute, Northeastern University, Boston, MA 02115 ABSTRACT Iron oxide nanoparticles are used for contrast enhancement in magnetic resonance imaging (MRI). We have prepared gold-coated iron oxide nanoparticles that show no change in their superparamagnetic behavior as a consequence of coating. Their potential use as MRI contrast agents was investigated by monitoring their T2 relaxation time with concentration. Cytotoxicity of these nanoparticles was also studied. The results of these studies are presented. INTRODUCTION Nanoparticles are increasingly being used in biomedicine [1]. A few of the applications suggested for magnetic nanoparticles are its use as sensing agents, in separation assays using their magnetophoretic properties, as drug delivery agent, in hyperthermia treatments [2] and in magnetic resonance imaging (MRI) contrast enhancement [3,4]. MRI technique is used to image soft tissue and utilizes contrast enhancing agents to improve imaging. Gadolinium containing compounds are used as positive contrast agents and signal enhancement is achieved through T1 relaxation. Use of positive contrast agents in the form of superparamagnetic iron oxide particles results in T2 relaxation and this results in signal enhancement. Superparamagnetic iron oxide-based particles are generally small, in the range of nanometers, and are functionalized with various ligands such as TAT peptide [5], transferrin, and folate [6] for detection of tumor cells. Functionalized magnetic nanoparticles provide a unique platform for molecular imaging as they can be detected by conventional MRI methods, can be “tailored” for specific signal recognition, and can be targeted to the disease site based on the enhanced permeability and retention effect of the tumor vasculature. When the size of the nanoparticles are very small (<300 nm), in addition to T2 relaxation, T1 relaxation is also seen. To further improve the specificity of these iron oxide nanoparticles to target a site in the body, such as a specific tumor, it is important to have control on the surface properties of the nanoparticles. The surface of the nanoparticles should be flexible enough to be able to modify with a unique antibody to target only the site of interest. We have used a gold shell on the iron oxide nanoparticle to achieve this. Conjugation of gold nanoparticle surfaces to various antibodies is tunable, highly controlled and very well established. Thus introducing a thin shell of gold on iron oxide nanoparticles to exploit the magnetic property of the iron oxide and site- specificity of gold shell, through suitable antibodies, will open a new class of MRI contrast agents. Additionally, polyethylene glycol (PEG) spacers can be introduced to help improve flexibility and the circulation in plasma [7]. EXPERIMENTAL METHODS Synthesis and characterization of iron oxide- gold core-shell nanoparticles The Fe 3 O 4 nanoparticles was prepared by first dissolving the Fe (II) and Fe (III) chloride salts in a dilute acid solution [8]. The precipitation of Fe 3 O 4 nanoparticles was then carried out by reduction of this salt solution by sodium hydroxide. The Fe 3 O 4 nanoparticles were then oxidized in boiling diluted acid to form the core γ-Fe 2 O 3 nanoparticles. Iterative hydroxylamine seeding procedure was followed to coat the nanoparticles with gold. In this method, to form the gold coating, sodium citrate solution was added to an small portion of iron oxide nanoparticles. The solution was diluted and aliquots of HAuCl 4 and excess hydroxylamine were added incrementally. This process was repeated until a uniform coating of gold was achieved on the iron oxide nanoparticles. Only the gold-coated iron oxide nanoparticles were separated by repeated centrifugation and magnetic separation from the solution containing a mixture of unreacted, excess material and gold nanoparticles. The gold-coated iron oxide nanoparticles were characterized by UV-vis absorption spectroscopy and transmission electron microscopy. Samples for TEM were prepared by allowing a drop of the nanoparticle suspension to be air-dried on a carbon-coated copper TEM grid. Magnetic Susceptibility Measurement Magnetic susceptibility was measured using Quantum Design MPMS XL-5 SQUID magnetometer both under field cooled and zero field cooled conditions. NSTI-Nanotech 2005, www.nsti.org, ISBN 0-9767985-0-6 Vol. 1, 2005 328