alexa Characterization and in vitro and in vivo testing of CB2-receptor- and NGAL-targeted paramagnetic micelles for molecular MRI of vulnerable atherosclerotic plaque.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): te Boekhorst BC, Bovens SM, RodriguesFeo J, Sanders HM, van de Kolk CW,

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Abstract PURPOSE: 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. This article was published in Mol Imaging Biol and referenced in Journal of Bioequivalence & Bioavailability

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