AVS 54th International Symposium
    Magnetic Interfaces and Nanostructures Wednesday Sessions
       Session MI-WeM

Paper MI-WeM13
Surface Functionalization of Single Iron Oxide Magnetic Nanoparticles (SPIONs) for Targeted Magnetic Resonance Imaging (MRI)

Wednesday, October 17, 2007, 12:00 pm, Room 619

Session: Magnetic Thin Films and Nanostructures
Presenter: E. Amstad, ETH Zurich, Switzerland
Authors: E. Amstad, ETH Zurich, Switzerland
E. Reimhult, ETH Zurich, Switzerland
S. Zurcher, ETH Zurich, Switzerland
J.A. Hamilton, Boston University Medical Campus
J.Y. Wong, Boston University
M. Textor, ETH Zurich, Switzerland
Correspondent: Click to Email

Commercially available negative magnetic resonance (MR) contrast agents often consist of multiple iron oxide cores embedded in a macromolecular matrix such as dextran. An alternative to the reversibly binding dextran is PEG-gallol or PEG-dopamine. The latter two molecules have a considerably higher binding affinity towards iron oxide nanoparticles compared to dextran, leading to enhanced particle stability and smaller particle diameters. Because PEG-gallol and PEG-dopamine adsorb on iron oxide in a well defined way, particles can be stabilized individually. Moreover, surface modifications of such PEGylated particles can be achieved by using PEG-chains that bear functional groups. Superparamagnetic iron oxide nanoparticles have been synthesized by an aqueous precipitation reaction and were stabilized individually using PEG-gallol and PEG-dopamine. Particle size, thermal stability and magnetic properties of these individually stabilized PEGylated particles have been compared with Feridex, a commercially available negative MR-contrast agent. To functionalize the former particles, iron oxide cores were coated with a combination of biotinylated PEG-dopamine and PEG-gallol. Neutravidin, a biotin-binding protein, served as a linker between the PEGylated particles bearing biotin sites and biotinylated functional groups. Neutravidin is an attractive linker for research purposes because any biotinylated ligand can be attached to it. Moreover, the number of ligands bound to one particle can easily be varied if neutravidin is used as an intermediate layer. In a first approach, these neutravidin coated PEGylated nanoparticles were targeted against atherosclerotic sites by attaching a custom-synthesized biotinylated peptide sequence to them.1 E-selectin is a transmembrane protein expressed on inflamed endothelial cells.2 It thus is an early marker for atherosclerosis. The blood half-life time of these functionalized superparamagnetic iron oxide nanoparticles has been determined in vivo in rabbits using magnetic resonance imaging (MRI).

1 Martens, C.L., et al., Peptides Which Bind to E-Selectin and Block Neutrophil Adhesion. Journal of Biological Chemistry, 1995. 270(36): p. 21129-21136.
2 Choudhury, R.P., V. Fuster, and Z.A. Fayad, Molecular, cellular and functional imaging of atherothrombosis. Nature Reviews Drug Discovery, 2004. 3(11): p. 913-925.