title: Annexin A5-functionalized bimodal nanoparticles for MRI and fluorescence imaging of atherosclerotic plaques.
abstract: Apoptosis and macrophage burden are believed to correlate with atherosclerotic plaque vulnerability and are therefore considered important diagnostic and therapeutic targets for atherosclerosis. These cell types are characterized by the exposure of phosphatidylserine (PS) at their surface. In the present study, we developed and applied a small micellar fluorescent annexin A5-functionalized nanoparticle for noninvasive magnetic resonance imaging (MRI) of PS exposing cells in atherosclerotic lesions. Annexin A5-mediated target-specificity was confirmed with ellipsometry and in vitro binding to apoptotic Jurkat cells. In vivo T(1)-weighted MRI of the abdominal aorta in atherosclerotic ApoE(-/-) mice revealed enhanced uptake of the annexin A5-micelles as compared to control-micelles, which was corroborated with ex vivo near-infrared fluorescence images of excised whole aortas. Confocal laser scanning microscopy (CLSM) demonstrated that the targeted agent was associated with macrophages and apoptotic cells, whereas the nonspecific control agent showed no clear uptake by such cells. In conclusion, the annexin A5-conjugated bimodal micelles displayed potential for noninvasive assessment of cell types that are considered to significantly contribute to plaque instability and therefore may be of great value in the assessment of atherosclerotic lesion phenotype.
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. gtilborg@gmail.com
authors.forename: Geralda A F
authors.initials: GA
authors.lastname: van Tilborg
authors.forename: Esad
authors.initials: E
authors.lastname: Vucic
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: David P
authors.initials: DP
authors.lastname: Cormode
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Mani
authors.forename: Torjus
authors.initials: T
authors.lastname: Skajaa
authors.forename: Chris P M
authors.initials: CP
authors.lastname: Reutelingsperger
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000737:chemistry*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001692:Biological Transport; D003287:Contrast Media; D005682:Gadolinium / Q000737:chemistry; D055786:Gene Knockout Techniques; D006801:Humans; D019169:Jurkat Cells; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008823:Micelles; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging / Q000379:methods*; D058726:Nanoconjugates / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology
chemical_list: D017304:Annexin A5; D001057:Apolipoproteins E; D003287:Contrast Media; D008823:Micelles; D058726:Nanoconjugates; D010718:Phosphatidylserines; D005682:Gadolinium
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