Intracellular dynamics of superparamagnetic iron oxide nanoparticles for magnetic particle imaging

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are a foundational platform for a variety of biomedical applications. Of particular interest is Magnetic Particle Imaging (MPI), which is a growing area of research and development due to its advantages including high resolution and sensitivity with positive contrast and without ionizing radiation. Significant work has been previously accomplished in the area of in vivo optimization of SPIONs for MPI as well as their biodistribution in and clearance from the body. However, little is known about the dynamics of SPIONs on the sub-cellular level. It is important to understand how the magnetic signal from SPIONs in MPI is affected by internalization within cells as physical and magnetic properties of SPIONs may be subject to changes. Here considerations must be made for the complex and close-packed nature of organelles and cellular material inside of the cell membrane. This work shows a clear decrease in magnetic performance of SPIONs after internalization and a systematic consideration of applicable factors that affect SPION signal generation, including microstructure, environment, and interparticle interactions. It is observed that microstructure is unchanged after internalization and surrounding environment plays little to no role in magnetic response for the SPIONs studied here. Interparticle interactions described by magnetostatic coupling of SPIONs held in close proximity to one another after internalization are shown to be the dominant cause of decreased magnetic performance in cells. These conclusions have been drawn from transmission electron microscopy (TEM) image analysis at relevant length scales, experimentally prepared and characterized SPIONs in varied environmental conditions, and theoretical modeling with Monte Carlo simulations. The addition of steric bulk to SPIONs is explored as an approach to recovering magnetic performance after internalization in cells. These results are promising for in vivo targeting, diagnostic, and cell tracking applications in MPI.