Development of europium doped core-shell silica cobalt ferrite functionalized nanoparticles for magnetic resonance imaging

Acta Biomater. 2017 Feb:49:507-520. doi: 10.1016/j.actbio.2016.11.071. Epub 2016 Dec 1.

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-1 and r2=419.52mM-1s-1 (in saline) and r2=736.57mM-1s-1 and 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-1 in saline) and paralleled data sets obtained for T2 magnetic resonance imaging. We now provide a developmental opportunity to employ these novel particles for theranostic drug distribution and efficacy evaluations.

Statement of significance: 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.

Keywords: Biodistribution; Cobalt ferrite; Magnetic resonance imaging; Monocyte-macrophages; Multimodal imaging; Nanoprobes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cobalt / chemistry*
  • Endocytosis
  • Europium / chemistry*
  • Ferric Compounds / chemistry*
  • Folic Acid / chemistry
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism
  • Macrophages / ultrastructure
  • Magnetic Resonance Imaging*
  • Male
  • Microscopy, Atomic Force
  • Microscopy, Confocal
  • Monocytes / cytology
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Rats, Sprague-Dawley
  • Silicon Dioxide / chemistry*
  • Spectroscopy, Fourier Transform Infrared
  • Thermogravimetry
  • Tissue Distribution

Substances

  • Ferric Compounds
  • cobalt ferrite
  • Cobalt
  • Europium
  • Silicon Dioxide
  • Folic Acid