Flash nanoprecipitation of magnetic particle imaging tracers with tunable performance

Magnetic particle imaging (MPI) is a novel biomedical imaging modality where biocompatible magnetic nanoparticle (MNP) tracers produce a quantitative signal for imaging applications like pharmacokinetics studies, blood pooling, cell tracking, and more. Improvements to tracer performance are generally made through the alteration of the synthesis mechanism and post-synthesis surface modification tailored to different applications. However, relying on synthesis alone to modify MPI performance can be difficult and time consuming. This study utilized flash nanoprecipitation, a method of MNP encapsulation, to vary the MPI performance of tracers. Herein, composite nanoparticle tracers were produced by precipitating hydrophobic iron oxide nanoparticles and homopolymer in water and stabilizing them with an amphiphilic block copolymer. By increasing the concentration of homopolymer used in precipitation, composite nanoparticle tracers with a range of physical properties and MPI performances were obtained, until a peak MPI performance was achieved and after which additional homopolymer did not further improve performance. Two pre-clinical applications of this work were demonstrated; the first was an in vivo imaging study and the second was color MPI. Intravenous injections show accumulation of two formulations in the liver and spleen after 24 hours, with MPI performance matching trends previously identified. Color MPI, an application of MPI whereby the signal from two MNP tracers can be separated into the signal contribution from each particle, allows for simultaneous tracking of multiple labelled species. Here, it was demonstrated using a 3D-printed mouse phantom mimicking accumulation of a two-formulation mixture in the liver, and individual particle formulations accumulating in the brain and hind flank tumor. The ratio of particles in each location was determined from the image and were comparable to ground truth values. This work demonstrates the ability of FNP to produce tunable MPI tracers, unlocking a range of applications, including pre-clinical imaging and color MPI.