Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging

摘要

Iron oxide nanoparticles have been extensively used as T₂ contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r₂ relaxivity. Recent studies show that Fe₅C₂ 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 T₂ contrast agent. To this end, we improve the synthetic and surface modification methods of Fe₅C₂ nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe₅C₂ 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 r₂ relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe₅C₂ nanoparticles showed comparable r₂, the casein coating led to an r₂ enhancement by more than 2 fold. In particular, casein coated 22 nm Fe₅C₂ nanoparticle show a striking r₂ of 973 mM-1s-1, which is one of the highest among all of the T₂ contrast agents reported to date. Small animal studies confirmed the advantage of Fe₅C₂ nanoparticles over iron oxide nanoparticles in inducing hypointensities on T₂-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe₅C₂ 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.