title: Rapid binding of electrostatically stabilized iron oxide nanoparticles to THP-1 monocytic cells via interaction with glycosaminoglycans.
abstract: 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.
authors: Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité, Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany. antje.ludwig@charite.de
authors: Antje
authors: A
authors: Ludwig
authors: Wolfram C
authors: WC
authors: Poller
authors: Kera
authors: K
authors: Westphal
authors: Susann
authors: S
authors: Minkwitz
authors: Gisela
authors: G
authors: Lättig-Tünnemann
authors: Susanne
authors: S
authors: Metzkow
authors: Karl
authors: K
authors: Stangl
authors: Gert
authors: G
authors: Baumann
authors: Matthias
authors: M
authors: Taupitz
authors: Susanne
authors: S
authors: Wagner
authors: Jörg
authors: J
authors: Schnorr
authors: Verena
authors: V
authors: Stangl
mesh_terms: D002460:Cell Line; D003287:Contrast Media / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008854:Microscopy, Electron; D009000:Monocytes / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000175:diagnosis
chemical_list: D003287:Contrast Media; D003911:Dextrans; D006025:Glycosaminoglycans; D058185:Magnetite Nanoparticles; C065507:ferumoxides