Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow

E. A. Ferrante, J. E. Pickard, J. Rychak, A. Klibanov, K. Ley

Research output: Contribution to journalArticlepeer-review

132 Scopus citations


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 languageEnglish (US)
Pages (from-to)100-107
Number of pages8
JournalJournal of Controlled Release
Issue number2
StatePublished - Dec 3 2009
Externally publishedYes


  • Microbubbles
  • P-selectin
  • Targeting
  • Ultrasound contrast
  • VCAM-1

ASJC Scopus subject areas

  • Pharmaceutical Science


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