TY - JOUR
T1 - Characterization and in vitro and in vivo testing of CB2-receptor- and NGAL-targeted paramagnetic micelles for molecular MRI of vulnerable atherosclerotic plaque
AU - te Boekhorst, B.C.M.
AU - Bovens, S.M.
AU - Rodrigues-Feo, J.
AU - Sanders, H.M.
AU - van de Kolk, C.W.A.
AU - de Kroon, A.I.
AU - Cramer, M.J.M.
AU - Doevendans, P.A.F.M.
AU - ten Hove, M.
AU - Pasterkamp, G.
AU - van Echteld, C.J.A.
PY - 2010
Y1 - 2010
N2 - Atherosclerotic plaque macrophages express the peripheral cannabinoid receptor (CB2-R) and promote fibrous cap degradation by secretion of neutrophil gelatinase-associated lipocalin 2 (NGAL). In this study, we report the preparation, characterization, and in vitro and in vivo testing of double-labeled (MR and fluorescent) CB2-R- and NGAL-targeted micelles.
Procedures/Results
Specific CB2-R agonists or antibodies directed to 24p3 (mouse homolog of NGAL) were incorporated into di-oleoyl-polyethylene glycol-phosphatidylethanolamine 1000 (DOPE-PEG1000) micelles or di-stearoyl-polyethylene glycol-phosphatidylethanolamine 2000 (DSPE-PEG2000) micelles. The hydrodynamic diameter, determined by dynamic light scattering, was 16.5 and 19.0 nm for CB2-R-targeted DOPE-PEG1000 and DSPE-PEG2000 micelles, respectively, and 23.0 nm for Ab-conjugated DSPE-PEG2000 micelles. In vitro and in vivo MRI and fluorescence microscopy showed specific binding of CB2-R-targeted and 24p3-targeted micelles to in vitro systems and to aortic plaque in apoE−/−/eNOS−/− mice, respectively.
Conclusions
CB2-R- and NGAL-targeted micelles show promise as tools for in vivo characterization of vulnerable plaque
AB - Atherosclerotic plaque macrophages express the peripheral cannabinoid receptor (CB2-R) and promote fibrous cap degradation by secretion of neutrophil gelatinase-associated lipocalin 2 (NGAL). In this study, we report the preparation, characterization, and in vitro and in vivo testing of double-labeled (MR and fluorescent) CB2-R- and NGAL-targeted micelles.
Procedures/Results
Specific CB2-R agonists or antibodies directed to 24p3 (mouse homolog of NGAL) were incorporated into di-oleoyl-polyethylene glycol-phosphatidylethanolamine 1000 (DOPE-PEG1000) micelles or di-stearoyl-polyethylene glycol-phosphatidylethanolamine 2000 (DSPE-PEG2000) micelles. The hydrodynamic diameter, determined by dynamic light scattering, was 16.5 and 19.0 nm for CB2-R-targeted DOPE-PEG1000 and DSPE-PEG2000 micelles, respectively, and 23.0 nm for Ab-conjugated DSPE-PEG2000 micelles. In vitro and in vivo MRI and fluorescence microscopy showed specific binding of CB2-R-targeted and 24p3-targeted micelles to in vitro systems and to aortic plaque in apoE−/−/eNOS−/− mice, respectively.
Conclusions
CB2-R- and NGAL-targeted micelles show promise as tools for in vivo characterization of vulnerable plaque
U2 - 10.1007/s11307-010-0323-z
DO - 10.1007/s11307-010-0323-z
M3 - Article
SN - 1536-1632
VL - 12
SP - 635
EP - 651
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 6
ER -