(136e) Tailoring Spions through Polymer Coating Modifications for Cell Labeling and Tracking with Magnetic Particle Imaging (MPI)

The use of adoptive T cell therapy has growing interest due to its promise for cancer immunotherapy. Studies suggest treatment outcomes correlate with the localization and persistence of these transferred T cells to tumor sites and in the peripheral blood. Thus, biodistribution information of T cells at different time points during therapy would be of use to clinicians. For this reason, modalities to accurately identify and quantify transferred cells in vivo are needed.

Magnetic Particle Imaging (MPI) addresses the need for quantitative tracking of cells in vivo using magnetic nanoparticle tracers. These tracers produce a biorthogonal signal, allowing for unambiguous and direct quantification. If these tracers effectively label T cells, their localization within the patient can be correlated with cell distribution. Using MPI tracers has extreme promise for tracking cell distribution in vivo longitudinally. Our group seeks to improve tracer signal per mass, signal resolution, and tracer surface chemistries for improved cell labeling to progress MPI tracer development for cell tracking purposes.

Particles are first synthesized through a thermal decomposition batch process which yields monodisperse magnetic Fe₃O₄ nanoparticles coated in oleic acid. To be useful in biomedical applications, a polymer coating surrounding the particles is necessary to render them colloidally stable in aqueous media, including cell culture media. Our strategy also introduces unreacted anchor sites near the surface of the particle for further polymer addition and thus additional particle modifications. Polymer choice will provide modularity in particle coating, allowing us to tune their surface chemistry and charge.

We have demonstrated the ability to coat tracers in poly(ethylene glycol) (PEG) and poly(maleic anhydride-alt-1-octadecene) (PMAO), demonstrate the colloidal stability of these particles in several solvents for multiple days, the ability to attach additional ligands onto the surface of the nanoparticles, modify nanoparticle surface charge, attach additional moieties to the hydrodynamic surface of the nanoparticle, and the ability to incubate primary T cells with these tracers in vitro to promote interaction and internalization. We are actively exploring several moieties to further modify the surface of the particle.

Future work will conjugate reactive groups to the nanoparticle surface and incubate functionalized SPIONs with cells of interest to demonstrate improved labeling capabilities. After, these labeled T cells will be introduced to an in vivo model and particle biodistribution will be assessed.