Magnetic nanomaterials for applications in magnetic resonance imaging and cancer stem cell biology
Jebb, Meghan Helen
Wilson, Lon J.
Doctor of Philosophy
Magnetic nanomaterials are uniquely suited for applications in biology and medicine. With size compatibility, tunable physical properties, and the capacity for external magnetic control, nanoscale magnetic particles have been exploited for drug delivery, hyperthermia-mediated cancer therapy, cell separation and isolation, and magnetic resonance imaging (MRI). This work explores several different nano-based materials for MRI and cancer cell isolation applications. First, Gd3+-loaded carbon nanotube capsules, or gadonanotubes (GNTs), have been analyzed by X-ray absorption spectroscopy to account for the structural contributions to their high MRI contrast enhancement properties. This work revealed the existence of small [Gd-O9] sites in the GNTs with short Gd-O (and thus Gd-H) bond lengths, which contribute to their high performance. Secondly, two new nanomaterials were developed, by loading paramagnetic Mn2+ ions into or onto ultra-short single-walled carbon nanotubes (US-tubes) or GNTs (manganonanotubes and manganogadonanotubes, MNTs and MGTs, respectively). With relaxivity (r1) values of 65 (MNT), 74 (MGT), and 110 (GNT) mM-1s-1 per ion and approximately 13-fold contrast enhancements in all cases over the free ions, US-tubes have been further confirmed as a universal platform for the enhancement of MRI contrast agent properties with the GNTs being the best r1 agents developed to date. Finally, a method for the isolation of quiescent breast cancer cells has been developed, using iron oxide nanoparticles (IONs) as intracellular labels. Once isolated, functional assays were employed to characterize the drug resistance and stem-like nature of the quiescent subpopulation. The project has thus demonstrated how a magnetic nanomaterial-facilitated procedure can be exploited to probe fundamental questions in cancer stem cell biology.