Non-invasively differentiating extent of liver fibrosis by visualizing hepatic integrin αvβ3 expression with an MRI modality in mice

Feng Li, Huihui Yan, Jiyao Wang, Cong Li, Jian Wu, Shengdi Wu, Shengxiang Rao, Xihui Gao, Qu Jin

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Aims To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis. Methods Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment. Results Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis. Conclusion The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.

Original languageEnglish (US)
Pages (from-to)162-174
Number of pages13
JournalBiomaterials
Volume102
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

Magnetic resonance
Integrins
Liver Cirrhosis
Liver
Nanoprobes
Magnetic Resonance Imaging
Imaging techniques
Dendrimers
Thioacetamide
Hepatic Stellate Cells
Arginine
Aspartic Acid
Glycine
Labeling
Amino acids
Acids

Keywords

  • Hepatic stellate cells
  • Integrin αvβ3
  • Liver fibrosis
  • MRI modality
  • Nanoprobe

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Non-invasively differentiating extent of liver fibrosis by visualizing hepatic integrin αvβ3 expression with an MRI modality in mice. / Li, Feng; Yan, Huihui; Wang, Jiyao; Li, Cong; Wu, Jian; Wu, Shengdi; Rao, Shengxiang; Gao, Xihui; Jin, Qu.

In: Biomaterials, Vol. 102, 01.09.2016, p. 162-174.

Research output: Contribution to journalArticle

Li, Feng ; Yan, Huihui ; Wang, Jiyao ; Li, Cong ; Wu, Jian ; Wu, Shengdi ; Rao, Shengxiang ; Gao, Xihui ; Jin, Qu. / Non-invasively differentiating extent of liver fibrosis by visualizing hepatic integrin αvβ3 expression with an MRI modality in mice. In: Biomaterials. 2016 ; Vol. 102. pp. 162-174.
@article{b33203d6a10c4fdd8c7bee4cfcecf9a4,
title = "Non-invasively differentiating extent of liver fibrosis by visualizing hepatic integrin αvβ3 expression with an MRI modality in mice",
abstract = "Aims To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis. Methods Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment. Results Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis. Conclusion The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.",
keywords = "Hepatic stellate cells, Integrin αvβ3, Liver fibrosis, MRI modality, Nanoprobe",
author = "Feng Li and Huihui Yan and Jiyao Wang and Cong Li and Jian Wu and Shengdi Wu and Shengxiang Rao and Xihui Gao and Qu Jin",
year = "2016",
month = "9",
day = "1",
doi = "10.1016/j.biomaterials.2016.06.026",
language = "English (US)",
volume = "102",
pages = "162--174",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Non-invasively differentiating extent of liver fibrosis by visualizing hepatic integrin αvβ3 expression with an MRI modality in mice

AU - Li, Feng

AU - Yan, Huihui

AU - Wang, Jiyao

AU - Li, Cong

AU - Wu, Jian

AU - Wu, Shengdi

AU - Rao, Shengxiang

AU - Gao, Xihui

AU - Jin, Qu

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Aims To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis. Methods Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment. Results Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis. Conclusion The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.

AB - Aims To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis. Methods Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment. Results Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis. Conclusion The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.

KW - Hepatic stellate cells

KW - Integrin αvβ3

KW - Liver fibrosis

KW - MRI modality

KW - Nanoprobe

UR - http://www.scopus.com/inward/record.url?scp=84975778572&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975778572&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2016.06.026

DO - 10.1016/j.biomaterials.2016.06.026

M3 - Article

C2 - 27341269

AN - SCOPUS:84975778572

VL - 102

SP - 162

EP - 174

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -