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

73 Citations (Scopus)

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

Fingerprint

Molecular imaging
Molecular Imaging
Contrast Media
Ultrasonography
Ultrasonics
Ligands
Microbubbles
Adhesion
Complement Activation
Bearings (structural)
Chemical activation
Radiation
Endothelial cells
Human Umbilical Vein Endothelial Cells
Buoyancy
Cell Adhesion
Integrins
Peptides

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

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

A stimulus-responsive contrast agent for ultrasound molecular imaging. / Borden, Mark A.; Zhang, Hua; Gillies, Robert J.; Dayton, Paul A.; Ferrara, Katherine W.

In: Biomaterials, Vol. 29, No. 5, 02.2008, p. 597-606.

Research output: Contribution to journalArticle

Borden, MA, Zhang, H, Gillies, RJ, Dayton, PA & Ferrara, KW 2008, 'A stimulus-responsive contrast agent for ultrasound molecular imaging', Biomaterials, vol. 29, no. 5, pp. 597-606. https://doi.org/10.1016/j.biomaterials.2007.10.011
Borden, Mark A. ; Zhang, Hua ; Gillies, Robert J. ; Dayton, Paul A. ; Ferrara, Katherine W. / A stimulus-responsive contrast agent for ultrasound molecular imaging. In: Biomaterials. 2008 ; Vol. 29, No. 5. pp. 597-606.
@article{6b958958ba434c35ab4ddae2e55795df,
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 = "Angiogenesis, Complement, Immune response, Molecular imaging, RGD peptide",
author = "Borden, {Mark A.} and Hua Zhang and Gillies, {Robert J.} and Dayton, {Paul A.} and Ferrara, {Katherine W.}",
year = "2008",
month = "2",
doi = "10.1016/j.biomaterials.2007.10.011",
language = "English (US)",
volume = "29",
pages = "597--606",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "5",

}

TY - JOUR

T1 - A stimulus-responsive contrast agent for ultrasound molecular imaging

AU - Borden, Mark A.

AU - Zhang, Hua

AU - Gillies, Robert J.

AU - Dayton, Paul A.

AU - Ferrara, Katherine W.

PY - 2008/2

Y1 - 2008/2

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Complement

KW - Immune response

KW - Molecular imaging

KW - RGD peptide

UR - http://www.scopus.com/inward/record.url?scp=36048931701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36048931701&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2007.10.011

DO - 10.1016/j.biomaterials.2007.10.011

M3 - Article

C2 - 17977595

AN - SCOPUS:36048931701

VL - 29

SP - 597

EP - 606

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 5

ER -