Casein-Coated Fe(5)C(2) Nanoparticles with Superior r(2) Relaxivity for Liver-Specific Magnetic Resonance Imaging

Iron oxide nanoparticles have been extensively used as T(2) contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r(2) relaxivity. Recent studies show that Fe(5)C(2) nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T(2) contrast agent. To this end, we improve the synthetic and surface modification methods of Fe(5)C(2) nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe(5)C(2) nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r(2) relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe(5)C(2) nanoparticles showed comparable r(2), the casein coating led to an r(2) enhancement by more than 2 fold. In particular, casein coated 22 nm Fe(5)C(2) nanoparticle show a striking r(2) of 973 mM(-1)s(-1), which is one of the highest among all of the T(2) contrast agents reported to date. Small animal studies confirmed the advantage of Fe(5)C(2) nanoparticles over iron oxide nanoparticles in inducing hypointensities on T(2)-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe(5)C(2) nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles.