Document Detail


Annexin A5-functionalized bimodal nanoparticles for MRI and fluorescence imaging of atherosclerotic plaques.
MedLine Citation:
PMID:  20804153     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Geralda A F van Tilborg; Esad Vucic; Gustav J Strijkers; David P Cormode; Venkatesh Mani; Torjus Skajaa; Chris P M Reutelingsperger; Zahi A Fayad; Willem J M Mulder; Klaas Nicolay
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  21     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-20     Completed Date:  2011-01-31     Revised Date:  2011-10-20    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1794-803     Citation Subset:  IM    
Affiliation:
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. gtilborg@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Annexin A5 / chemistry*
Apolipoproteins E / deficiency,  genetics
Biological Transport
Contrast Media / diagnostic use
Gadolinium / chemistry
Gene Knockout Techniques
Humans
Jurkat Cells
Magnetic Resonance Imaging / methods*
Male
Mice
Micelles
Microscopy, Fluorescence
Molecular Imaging / methods*
Nanoconjugates / chemistry*,  diagnostic use*
Phosphatidylserines / chemistry
Plaque, Atherosclerotic / diagnosis*,  metabolism*,  pathology
Grant Support
ID/Acronym/Agency:
K99 EB012165-01/EB/NIBIB NIH HHS; R01 EB009638-07/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Apolipoproteins E; 0/Contrast Media; 0/Micelles; 0/Nanoconjugates; 0/Phosphatidylserines; 7440-54-2/Gadolinium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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