title: Cellular imaging of inflammation in atherosclerosis using magnetofluorescent nanomaterials.
abstract: OBJECTIVE
  Magnetofluorescent nanoparticles (MFNPs) offer the ability to image cellular inflammation in vivo. To better understand their cellular targeting and imaging capabilities in atherosclerosis, we investigated prototypical dextran-coated near-infrared fluorescent MFNPs in the apolipoprotein E-deficient (apo E-/-) mouse model.
  
  
  RESULTS
  In vitro MFNP uptake was highest in activated murine macrophages (p < .001). Apo E-/- mice (n = 11) were next injected with the MFNP (15 mg/kg iron) or saline. In vivo magnetic resonance imaging (MRI) demonstrated strong plaque enhancement by the MFNPs (p < .001 vs. saline), which was confirmed by multimodality ex vivo MRI and fluorescence reflectance imaging. On fluorescence microscopy, MFNPs were found in cellular-rich areas of atheroma and colocalized with immunofluorescent macrophages over endothelial cells and smooth muscle cells (p < .001).
  
  
  CONCLUSIONS
  Here we show that (1) the in vitro and in vivo cellular distribution of atherosclerosis-targeted MFNPs can be quantified by using fluorescence imaging methods; (2) in atherosclerosis, dextranated MFNPs preferentially target macrophages; and (3) MFNP deposition in murine atheroma can be noninvasively detected by in vivo MRI. This study thus provides a foundation for using MFNPs to image genetic and/or pharmacological perturbations of cellular inflammation in experimental atherosclerosis and for the future development of novel targeted nanomaterials for atherosclerosis.
authors.affiliation: Harvard Medical School, Charlestown, MA 02129, USA. fjaffer@partners.org
authors.forename: Farouc A
authors.initials: FA
authors.lastname: Jaffer
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: David
authors.initials: D
authors.lastname: Sosnovik
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kelly
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008163:Luminescent Measurements; D008262:Macrophage Activation; D008264:Macrophages / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D018345:Mice, Knockout; D049329:Nanostructures; D019265:Spectroscopy, Near-Infrared