title: Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.
abstract: 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(-1)s(-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.
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
authors.forename: Taku A
authors.initials: TA
authors.lastname: Cowger
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Zhen
authors.affiliation: 2. Department of Chemistry, Wuhan University, Wuhan, Hubei, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Rink
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
authors.forename: Trever J
authors.initials: TJ
authors.lastname: Todd
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Wang
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Chen
authors.affiliation: 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA ; 3. Bio-Imaging Research Center, the University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D017554:Carbon Compounds, Inorganic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002364:Caseins / Q000378:metabolism; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003287:Contrast Media / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D058085:Iron Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D023421:Models, Animal; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D017554:Carbon Compounds, Inorganic; D002364:Caseins; D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D058085:Iron Compounds; C541825:iron carbide
keywords: casein; iron carbides; macrophages; magnetic nanoparticles; magnetic resonance imaging; surface modification