Document Detail

Rapid binding of electrostatically stabilized iron oxide nanoparticles to THP-1 monocytic cells via interaction with glycosaminoglycans.
MedLine Citation:
PMID:  23314954     Owner:  NLM     Status:  MEDLINE    
Magnetic resonance imaging (MRI) with contrast agents that target specific inflammatory components of atherosclerotic lesions has the potential to emerge as promising diagnostic modality for detecting unstable plaques. Since a high content of macrophages and alterations of the extracellular matrix are hallmarks of plaque instability, these structures represent attractive targets for new imaging modalities. In this study, we compared in vitro uptake and binding of electrostatically stabilized citrate-coated very small superparamagnetic iron oxide particles (VSOP) to THP-1 cells with sterically stabilized carboxydextran-coated Resovist(®). Uptake of VSOP in both THP-1 monocytic cells and THP-derived macrophages (THP-MΦ) was more efficient compared to Resovist(®) without inducing cytotoxicity or modifying normal cellular functions (no changes in levels of reactive oxygen species, caspase-3 activity, proliferation, cytokine production). Importantly, VSOP bound with high affinity to the cell surface and to apoptotic membrane vesicles. Inhibition of glycosaminoglycan (GAG) synthesis by glucose deprivation in THP-MΦ was associated with a significant reduction of VSOP attachment suggesting that the strong interaction of VSOP with the membranes of cells and apoptotic vesicles occurs via binding to negatively charged GAGs. These in vitro experiments show that VSOP-enhanced MRI may represent a new imaging approach for visualizing high-risk plaques on the basis of targeting pathologically increased GAGs or apoptotic membrane vesicles in atherosclerotic lesions. VSOP should be investigated further in appropriate in vivo experiments to characterize accumulation in unstable plaque.
Antje Ludwig; Wolfram C Poller; Kera Westphal; Susann Minkwitz; Gisela Lättig-Tünnemann; Susanne Metzkow; Karl Stangl; Gert Baumann; Matthias Taupitz; Susanne Wagner; Jörg Schnorr; Verena Stangl
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-12
Journal Detail:
Title:  Basic research in cardiology     Volume:  108     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-14     Completed Date:  2013-07-18     Revised Date:  2014-08-20    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  328     Citation Subset:  IM    
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MeSH Terms
Cell Line
Contrast Media / metabolism*
Dextrans / metabolism*
Glycosaminoglycans / metabolism
Macrophages / metabolism
Magnetic Resonance Imaging
Magnetite Nanoparticles / chemistry
Microscopy, Electron
Monocytes / metabolism*
Plaque, Atherosclerotic / diagnosis
Reg. No./Substance:
0/Contrast Media; 0/Glycosaminoglycans; 0/Magnetite Nanoparticles; G6N3J05W84/ferumoxides; K3R6ZDH4DU/Dextrans

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