title: Development of europium doped core-shell silica cobalt ferrite functionalized nanoparticles for magnetic resonance imaging.
abstract: The size, shape and chemical composition of europium (Eu3+) cobalt ferrite (CFEu) nanoparticles were optimized for use as a "multimodal imaging nanoprobe" for combined fluorescence and magnetic resonance bioimaging. Doping Eu3+ions into a CF structure imparts unique bioimaging and magnetic properties to the nanostructure that can be used for real-time screening of targeted nanoformulations for tissue biodistribution assessment. The CFEu nanoparticles (size ∼7.2nm) were prepared by solvothermal techniques and encapsulated into poloxamer 407-coated mesoporous silica (Si-P407) to form superparamagnetic monodisperse Si-CFEu nanoparticles with a size of ∼140nm. Folic acid (FA) nanoparticle decoration (FA-Si-CFEu, size ∼140nm) facilitated monocyte-derived macrophage (MDM) targeting. FA-Si-CFEu MDM uptake and retention was higher than seen with Si-CFEu nanoparticles. The transverse relaxivity of both Si-CFEu and FA-Si-CFEu particles were r2=433.42mM-1s-1and r2=419.52mM-1s-1(in saline) and r2=736.57mM-1s-1and r2=814.41mM-1s-1(in MDM), respectively. The results were greater than a log order-of-magnitude than what was observed at replicate iron concentrations for ultrasmall superparamagnetic iron oxide (USPIO) particles (r2=31.15mM-1s-1in saline) and paralleled data sets obtained for T2magnetic resonance imaging. We now provide a developmental opportunity to employ these novel particles for theranostic drug distribution and efficacy evaluations.
  
  
  
  A novel europium (Eu3+) doped cobalt ferrite (Si-CFEu) nanoparticle was produced for use as a bioimaging probe. Its notable multifunctional, fluorescence and imaging properties, allows rapid screening of future drug biodistribution. Decoration of the Si-CFEu particles with folic acid increased its sensitivity and specificity for magnetic resonance imaging over a more conventional ultrasmall superparamagnetic iron oxide particles. The future use of these particles in theranostic tests will serve as a platform for designing improved drug delivery strategies to combat inflammatory and infectious diseases.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, United States.
authors.forename: Bhavesh D
authors.initials: BD
authors.lastname: Kevadiya
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, United States.
authors.forename: Aditya N
authors.initials: AN
authors.lastname: Bade
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, Omaha, NE 68198-1045, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Woldstad
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, United States.
authors.forename: Benson J
authors.initials: BJ
authors.lastname: Edagwa
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, United States.
authors.forename: JoEllyn M
authors.initials: JM
authors.lastname: McMillan
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, Omaha, NE 68198-1045, United States.
authors.forename: Balasrinivasa R
authors.initials: BR
authors.lastname: Sajja
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, Omaha, NE 68198-1045, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Boska
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, United States. Electronic address: hegendel@unmc.edu.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000818:Animals; D003035:Cobalt / Q000737:chemistry*; D004705:Endocytosis; D005063:Europium / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; C569492:cobalt ferrite; D003035:Cobalt; D005063:Europium; D012822:Silicon Dioxide; D005492:Folic Acid
keywords: Biodistribution; Cobalt ferrite; Magnetic resonance imaging; Monocyte-macrophages; Multimodal imaging; Nanoprobes