Ultrasound radiation force modulates ligand availability on targeted contrast agents.

TitleUltrasound radiation force modulates ligand availability on targeted contrast agents.
Publication TypeJournal Article
Year of Publication2006
AuthorsBorden MA, Sarantos MR, Stieger SM, Simon SI, Ferrara KW, Dayton PA
JournalMolecular imaging
Volume5
Issue3
Pagination139-47
Date Published2006 Jul
ISSN1535-3508
KeywordsAnimals, Biological Availability, Cell Adhesion, Contrast Media, Diagnostic Imaging, Feasibility Studies, Flow Cytometry, Humans, Kidney, Leukocytes, Ligands, Male, Microbubbles, Models, Biological, Neutrophils, Rats, Rats, Sprague-Dawley
Abstract

Radiation force produced by low-amplitude ultrasound at clinically relevant frequencies remotely translates freely flowing microbubble ultrasound contrast agents over distances up to centimeters from the luminal space to the vessel wall in order to enhance ligand-receptor contact in targeting applications. The question arises as to how the microbubble shell might be designed at the molecular level to fully take advantage of such physical forces in targeted adhesion for molecular imaging and controlled therapeutic release. Herein, we report on a novel surface architecture in which the tethered ligand is buried in a polymeric overbrush. Our results, with biotin-avidin as the model ligand-receptor pair, show that the overbrush conceals the ligand, thereby reducing immune cell binding and increasing circulation persistence. Targeted adhesion is achieved through application of ultrasound radiation force to instantly reveal the ligand within a well-defined focal zone and simultaneously bind the ligand and receptor. Our data illustrate how the adhesive properties of the contrast agent surface can be reversibly changed, from stealth to sticky, through the physical effects of ultrasound. This technique can be combined with any ligand-receptor pair to optimize targeted adhesion for ultrasonic molecular imaging.

Alternate JournalMol Imaging