Cellular imaging of inflammation in atherosclerosis using magnetofluorescent nanomaterials.
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.
Jaffer
Farouc A
FA
Harvard Medical School, Charlestown, MA 02129, USA. fjaffer@partners.org
Nahrendorf
Matthias
M
Sosnovik
David
D
Kelly
Kimberly A
KA
Aikawa
Elena
E
Weissleder
Ralph
R
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