(118g) Surfactant Mediated Phase Transfer of Iron Oxide Nanoparticles

Magnetic nanoparticles are an attractive platform for imaging and drug delivery. Magnetic Particle Imaging (MPI) is a novel imaging modality that detects the signal of superparamagnetic iron oxide nanoparticles (SPIONs) as they respond to an applied magnetic field. The signal is quantitative, proportional to the iron mass, unambiguous, and unattenuated by tissue depth, which is an advantage compared to traditional imaging procedures. Designing SPIONs whose surface properties make them colloidally stable in tissue culture media and biocompatible with T cells will allow their use to track immune therapies in vivo. Adoptive cellular therapy (ACT), for example, is a type of immunotherapy that uses a patient’s own cells to target and destroy cancer cells. Clinical studies have suggested that the effectiveness of ACT in solid tumors is dependent on the accumulation and persistence of T cells at the tumor site. Therefore, using MPI to non-invasively track T cells will enable visualization of their distribution within a sample and help understand the mechanisms of action and failure of ACT immunotherapies.

Many of the methods used to synthesize nanoparticles develop them in organic solvents. The thermal decomposition of iron oleate used in our lab yields SPIONs with consistent physical and magnetic properties, but in a complex mixture of organic solvents and surfactants that provide stability under those conditions. Through a series of washes, most of the organic compounds can be removed, leaving behind hydrophobic SPIONs coated with a surfactant monolayer. However, SPIONs for biomedical applications need to maintain colloidal stability in aqueous media, as biological systems are mostly composed of water. The phase transfer of SPIONs from organic to aqueous media can be achieved with the help of surfactants which coat the surface to facilitate the effective transfer to water. Given the wide variety of surfactants available and the broad range of processing conditions that can be used to achieve phase transfer, the composition and process design parameter space is very large and high-throughput approaches are desirable.

Our goal is to develop a platform for high-throughput evaluation of surfactant double layer phase transfer compositions and processing conditions. In this study, we report initial progress using oleic acid (OA) to mediate the phase transfer of SPIONs from organic solution into water. Since OA is already present on the surface of as synthesized nanoparticles, the expectation is that additional OA will form a surfactant double layer (SDL). The SDL arranges in such a way that the hydrophobic tails interdigitate, and the hydrophilic heads are adsorbed on the SPION surface on one layer and interact outwardly with water molecules on the other layer. Phase transfer is achieved by vigorously mixing the organic phase containing the SPIONs with a volume of deionized water. This is followed by tip ultrasonication, which causes an oil-in-water emulsion to form, so that more of the SPIONs are in contact with water rather than aggregated within the oil droplets.

Initial studies suggest successful transfer of SPIONs to water. While the average SPION size observed using transmission electron microscopy (TEM) is ~20 nm in the organic solvent, the hydrodynamic sizes of the particles are much larger after transfer into water, suggesting aggregation. A positive relationship between addition of surfactant and improved transfer yield percentage has been observed. Conversely, our data suggests that lower amounts of OA achieve phase transfer of single particles. Ongoing work seeks to optimize phase transfer yield and reduce hydrodynamic size, evaluate stability of the resulting particles in T cell culture media, and evaluate phase transfer using combinations of surfactant to tune particle zeta potential, stability, and interaction with T cells.