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A stimulus-responsive contrast agent for ultrasound molecular imaging

Paper ID Volume ID Publish Year Pages File Format Full-Text
10045 660 2008 10 PDF Available
Title
A stimulus-responsive contrast agent for ultrasound molecular imaging
Abstract

Complement activation by targeting ligands is an important issue that governs the fate of targeted colloidal contrast agents for molecular imaging. Here, we extend previous work on a stimulus-responsive microbubble construct, in which the ligand is normally buried by a polymeric overbrush and transiently revealed by ultrasound radiation force, to show reduced complement activation and focused adhesion to cells using a physiological peptide ligand. Attachment of C3/C3b in vitro and production of soluble C3a anaphylotoxin in vitro and in vivo decreased significantly for the buried-ligand architecture vs. the conventional exposed-ligand motif and no-ligand control. Additionally, the buried-ligand architecture prevented adhesion of Arg–Gly–Tyr (RGD)-bearing microbubbles to integrin-expressing human umbilical vein endothelial cells (HUVEC) when driven by buoyancy in a static chamber, but it did not affect adhesion efficiency when activated by ultrasound radiation force pulses. These results show, for the first time, the molecular mechanism for reduced immunogenicity for the buried-ligand architecture and feasibility of targeting with this motif using a physiological ligand–receptor pair.

Keywords
Molecular imaging; RGD peptide; Angiogenesis; Complement; Immune response
First Page Preview
A stimulus-responsive contrast agent for ultrasound molecular imaging
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 5, February 2008, Pages 597–606
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering