Tuning Surface Coatings of Optimized Magnetite Nanoparticle Tracers for In Vivo Magnetic Particle Imaging

Surface coatings are important components of magnetic particle imaging (MPI) tracers - they preserve their key properties responsible for optimum tracer performance in physiological environments. In vivo, surface coatings form a physical barrier between the hydrophobic superparamagnetic iron oxide nanoparticles (SPION) cores and the physiological environment, and their design dictates the blood half-life and biodistribution of MPI tracers. Here, we show the effect of tuning poly(ethylene glycol) (PEG)-based surface coatings on both in vitro and in vivo (mouse model) MPI performance of SPIONs. Our results showed that varying PEG molecular weight had a profound impact on colloidal stability, characterized using dynamic light scattering, and the m'(H) response of SPIONs, measured in a 25 kHz/20 mTμ₀⁰_max magnetic particle spectrometer. Increasing PEG molecular weight from 5 to 20 kDa preserved colloidal stability and m'(H) response of ∼25 nm SPIONs - the optimum core diameter for MPI - in serum-rich cell culture medium for up to 24 h. Furthermore, we compared the in vivo circulation time of SPIONs as a function of hydrodynamic diameter and showed that clustered SPIONs can adversely affect blood half-life; critically, SPIONs with clusters had five times shorter blood half-life than individually coated SPIONs. We anticipate that the development of MPI SPION tracers with long blood half-lives have potential not only in vascular imaging applications, but also enable opportunities in molecular targeting and imaging - a critical step toward early cancer detection using the new MPI modality.