(813f) Structure-Relaxivity Relationships of Well-Defined Magnetite Clusters for Sensitive Magnetic Resonance Imaging

In the past decade, multifunctional magnetite nanocarriers that integrate therapeutic agents into a single system have attracted considerable interest in theranostics integrating drug delivery and drug biodistribution. Magnetic nanoparticles have long been recognized as T₂-contrast agents for MRI. We report colloidally-stable magnetite clusters with hydrophobic and hydrophilic cores, and controlled sizes and compositions. Discrete ~ 8 nm nanoparticles (M_s = 65 A.m²/kg) were synthesized by reducing iron (III) acetylacetonate in benzyl alcohol and their surfaces were subsequently modified to be hydrophobic by coating with oleic acid. A poly(ethylene glycol)-b-poly(D,L-lactide) block copolymer [mPEG(5 kDa)-b-PDLLA(10 kDa)] was synthesized by ring-opening polymerization of D,L-lactide in the presence of mPEG using stannous octoate as the catalyst. Hydrophobic-core clusters were prepared by rapid nanoprecipitation using an amphiphilic poly(D,L-lactide)-poly(ethylene oxide) diblock copolymer stabilizer. Nanoparticles with hydrodynamic diameters in the range of 100-150 nm and polydispersity indices less than 0.2 were obtained, as measured by dynamic light scattering. The transverse and longitudinal NMR relaxivities of the magnetite-loaded nanoparticles were ~ 200 s^-1.mM Fe^-1 and ~ 1 s^-1.mM Fe^-1 respectively. The transverse relaxivities enabled sensitive T₂-weighted MRI and the low longitudinal relaxivities are consistent with the hydrophobic nature of the cores of the nanoparticle clusters.

For the hydrophilic-core clusters, magnetite-poly(ethylene oxide-b-acrylate) complexes were synthesized, followed by crosslinking the amine tips of the H₂N-PEO corona with PEO diacrylate. The transverse relaxivities of the two classes of clusters correlated with particle sizes and compositions. Interestingly, the hydrophilic-core clusters had transverse relaxivities approaching the static dephasing limit of ~ 600 s^-1.mM Fe^-1 and were more than twice that of the hydrophobic-core clusters at similar sizes and compositions. We posit that the high magnetic field gradients accessible to water protons by diffusion within the core of the hydrophilic clusters lead to the higher relaxivities.