A stimulus-responsive contrast agent for ultrasound molecular imaging

Mark A. Borden, Hua Zhang, Robert J. Gillies, Paul A. Dayton, Katherine W. Ferrara

Research output: Contribution to journalArticle

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)597-606
Number of pages10
JournalBiomaterials
Volume29
Issue number5
DOIs
StatePublished - Feb 2008

Keywords

  • Angiogenesis
  • Complement
  • Immune response
  • Molecular imaging
  • RGD peptide

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'A stimulus-responsive contrast agent for ultrasound molecular imaging'. Together they form a unique fingerprint.

  • Cite this

    Borden, M. A., Zhang, H., Gillies, R. J., Dayton, P. A., & Ferrara, K. W. (2008). A stimulus-responsive contrast agent for ultrasound molecular imaging. Biomaterials, 29(5), 597-606. https://doi.org/10.1016/j.biomaterials.2007.10.011