(813e) Surface Functionalization of Iron Oxide Nanoparticles for Biological Encapsidation Applications

Super-paramagnetic iron oxide nanoparticles (SPIO) have been utilized for more than two decades as contrast agents for magnetic resonance imaging (MRI), but recent years in particular have seen a dramatic increase in the number of potential applications for these nanoparticles.  SPIO and SPIO-based constructs are being studied for a range of uses, including tumor imaging, drug delivery, and tissue repair.  However, many of these applications require that the SPIO be packaged within or otherwise fused to a larger biological construct while maintaining stability in a physiological environment.  Current approaches for functionalizing water-soluble SPIO generally result in relatively thick surface coatings that limit the size of SPIO that can be encapsidated; this, in turn, decreases the potential transverse relaxivities of the SPIO, rendering them less effective contrast agents.  Here we demonstrate a novel biphasic method for stabilizing organic SPIO in an aqueous environment.  This method minimizes the thickness of the nanoparticle surface coating to facilitate encapsidation within a biological construct of limited size and also maximizes transverse relaxivity.  Briefly, sonication creates interfacial surface area between an aqueous SPIO-receiving phase and an organic phase containing both the hydrophobic oleic acid-coated SPIO and amphipathic molecules that intercalate into the oleic acid layer to produce a new hydrophilic surface coating.  Following sonication, the resultant emulsion is phase-separated into its component layers via centrifugation, and the now-colored aqueous layer contains SPIO that have undergone successful phase transfer.  Various parameters including sonication time and intensity, aqueous buffer and composition, and different amphipathic molecules, were studied to optimize SPIO phase transfer while maximizing relaxivities.  This technique yields monodisperse, water-soluble SPIO with minimal coating thickness (< 3 nm) as measured by dynamic light scattering (DLS) and high transverse relaxivities (r₂ ≥ 200 mM_Fe^-1s^-1) via ¹H NMR.  Furthermore, the amphipathic coating molecules can be selected based on the desired SPIO surface charge and functional group (e.g. amine or carboxylic acid).  Thus, this functionalization technique, with fine control over the surface chemistry while minimizing the coating thickness, offers the ability to produce effective SPIO with the flexibility of being encapsidated within various biological constructs.