Engineering magnetic nanoparticle-based MRI contrast agents for molecular imaging

We have developed a novel magnetic iron oxide nanoparticle (MION)-based probe for detection of oligonucleotide hybridization. A PEG-phospholipid micelle-based coating was used to achieve water solubility, uniform size distribution, and functionalized surface for conjugation [1]. In this design, DNA oligonucleotides of varying length were conjugated to functionalized MIONs using chemical crosslinkers to create a stem-loop hairpin or random-coil structure. Hybridization to complementary oligonucleotides induced a conformational change from a closed structure (MIONs predicted to be in close proximity) to the open, double-stranded structure, resulting in a decrease in relaxivity (R2 = (1/T2)/[Fe]; mM-1*s-1) as measured by a 0.47T Bruker Minispec Analyzer MQ20. Numerical simulations (using a Monte Carlo technique) were done to further understand the effect of the distance between MIONs on relaxation characteristics of such magnetic probes. Experimentally observed decreases in relaxivity upon increase of distance between bound particles were consistent with the results of simulations. Previous work [2] has shown that clustering of magnetic nanoparticles is an effective method of detecting oligonucleotide hybridization. This work will help further elucidate the mechanisms and possible applications of molecular magnetic switches for molecular imaging using MRI.