Accounting for biological aggregation in heating and imaging of magnetic nanoparticles

Michael L Etheridge; Katie R Hurley; Jinjin Zhang; Seongho Jeon; Hattie L Ring; Christopher Hogan; Christy L Haynes; Michael Garwood; John C Bischof

doi:10.1142/S2339547814500198

Accounting for biological aggregation in heating and imaging of magnetic nanoparticles

Technology (Singap World Sci). 2014 Sep;2(3):214-228. doi: 10.1142/S2339547814500198.

Authors

Michael L Etheridge¹, Katie R Hurley², Jinjin Zhang³, Seongho Jeon⁴, Hattie L Ring⁵, Christopher Hogan⁴, Christy L Haynes², Michael Garwood⁶, John C Bischof¹

Affiliations

¹ Department of Mechanical Engineering, University of Minnesota, 111 Church Street SE, Minneapolis, MN 55455, USA. ; Department of Biomedical Engineering, University of Minnesota, 312 Church Street SE, Minneapolis, MN 55455, USA.
² Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, MN 55455, USA.
³ Center for Magnetic Resonance Research, University of Minnesota, 2021 Sixth Street SE, Minneapolis, MN 55455, USA. ; Department of Physics, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455, USA.
⁴ Department of Mechanical Engineering, University of Minnesota, 111 Church Street SE, Minneapolis, MN 55455, USA.
⁵ Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, MN 55455, USA. ; Center for Magnetic Resonance Research, University of Minnesota, 2021 Sixth Street SE, Minneapolis, MN 55455, USA.
⁶ Center for Magnetic Resonance Research, University of Minnesota, 2021 Sixth Street SE, Minneapolis, MN 55455, USA. ; Department of Radiology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, USA.

Abstract

Aggregation is a known consequence of nanoparticle use in biology and medicine; however, nanoparticle characterization is typically performed under the pretext of well-dispersed, aqueous conditions. Here, we systematically characterize the effects of aggregation on the alternating magnetic field induced heating and magnetic resonance (MR) imaging performance of iron oxide nanoparticles (IONPs) in non-ideal biological systems. Specifically, the behavior of IONP aggregates composed of ~10 nm primary particles, but with aggregate hydrodynamic sizes ranging from 50 nm to 700 nm, was characterized in phosphate buffered saline and fetal bovine serum suspensions, as well as in gels and cells. We demonstrate up to a 50% reduction in heating, linked to the extent of aggregation. To quantify aggregate morphology, we used a combination of hydrodynamic radii distribution, intrinsic viscosity, and electron microscopy measurements to describe the aggregates as quasifractal entities with fractal dimensions in the 1.8-2.0 range. Importantly, we are able to correlate the observed decrease in magnetic field induced heating with a corresponding decrease in longitudinal relaxation rate (R₁) in MR imaging, irrespective of the extent of aggregation. Finally, we show in vivo proof-of-principle use of this powerful new imaging method, providing a critical tool for predicting heating in clinical cancer hyperthermia.

Grants and funding

P41 EB015894/EB/NIBIB NIH HHS/United States