Abstract
To improve ultrasound contrast agents targeted to the adhesion molecules P-selectin and VCAM-1 for the purpose of molecular imaging of atherosclerotic plaques, perfluorocarbon-filled phospholipid microbubble contrast agents were coupled by a polyethylene glycol-biotin-streptavidin bridge with mAb MVCAM.A(429), a sialyl Lewisx polymer (PAA-sLex), or both (dual). Approximately three hundred thousand antibody molecules were coupled to the surface of each microbubble. Recombinant mouse P-selectin and/or VCAM-1 coated on flow chambers showed saturation of binding at approximately 15 ng/μl, resulting in 800 and 1200 molecules/μm2 for P-selectin and VCAM-1, respectively. Dual substrates coated with equal concentrations of P-selectin and VCAM-1 had site densities between 50 and 60% of single substrates. When microbubbles were perfused through flow chambers at 5 × 106 microbubbles/ml (wall shear stress from 1.5 to 6 dyn/cm2) dual-targeted microbubbles adhered almost twice as efficiently as single-targeted microbubbles at 6 dyn/cm2. The present study suggests that dual-targeted contrast agents may be useful for atherosclerotic plaque detection at physiologically relevant shear stresses.
Original language | English (US) |
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Pages (from-to) | 100-107 |
Number of pages | 8 |
Journal | Journal of Controlled Release |
Volume | 140 |
Issue number | 2 |
DOIs | |
State | Published - Dec 3 2009 |
Externally published | Yes |
Keywords
- Microbubbles
- P-selectin
- Targeting
- Ultrasound contrast
- VCAM-1
ASJC Scopus subject areas
- Pharmaceutical Science