An apoptosis-homing peptide-conjugated low molecular weight heparin-taurocholate conjugate with antitumor properties

Sang Mun Bae, Jong Ho Kim, Seung Woo Chung, Youngro Byun, Sang Yoon Kim, Byung Heon Lee, In-San Kim, Rang Woon Park

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Various angiogenesis inhibitors and apoptosis-targeting agents have been therapeutically applied in preclinical cancer models, some of which have been tested in clinical trials. In a previous study, we demonstrated that LHT7, a low molecular weight heparin (LMWH)-taurocholate conjugate, has strong antiangiogenic and tumor-suppressive activity and diminished anticoagulant properties. In this study, we developed LHT7-ApoPep-1, an apoptosis-homing peptide-conjugated variant of LHT7. LHT7-ApoPep-1 exhibited antiangiogenic activity in endothelial cell tube-formation assays and apoptotic cell-targeting ability in tumor cell binding assays; it also showed little toxicity toward healthy cells. Administration of LHT7-ApoPep-1 in mouse xenograft models of breast carcinoma delayed tumor growth compared to LHT7-only, and histological evaluations revealed decreased vessel formation and increased apoptotic area in tumor tissues. Moreover, an examination of LHT7-ApoPep-1-Cy7.5 localization within the body using in vivo live imaging showed accumulation at the tumor site of tumor-bearing mice, with a more prolonged circulation time and enhanced intensity compared to LHT7-Cy7.5. Inspection of the tumor microenvironment revealed that Cy5.5-labeled LHT7-ApoPep-1 was located on and near CD31-positive vessels in tumor tissue. We conclude that LHT7-ApoPep-1 has antiangiogenic and apoptosis-targeting properties and exerts antitumor effects by suppressing tumor vessel growth and homing to apoptotic cells within the tumor.

Original languageEnglish
Pages (from-to)2077-2086
Number of pages10
JournalBiomaterials
Volume34
Issue number8
DOIs
Publication statusPublished - 2013 Mar 1
Externally publishedYes

Fingerprint

Taurocholic Acid
Low Molecular Weight Heparin
Cell death
Peptides
Tumors
Molecular weight
Apoptosis
Neoplasms
Cells
Assays
Bearings (structural)
Heparin
Tissue
Angiogenesis Inhibitors
Tumor Microenvironment
Endothelial cells
Growth
Heterografts
Anticoagulants
Toxicity

Keywords

  • Angiogenesis
  • ApoPep-1-conjugated LMWH-taurocholate
  • Apoptosis
  • Homing peptide
  • In vivo imaging

ASJC Scopus subject areas

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

Cite this

An apoptosis-homing peptide-conjugated low molecular weight heparin-taurocholate conjugate with antitumor properties. / Bae, Sang Mun; Kim, Jong Ho; Chung, Seung Woo; Byun, Youngro; Kim, Sang Yoon; Lee, Byung Heon; Kim, In-San; Park, Rang Woon.

In: Biomaterials, Vol. 34, No. 8, 01.03.2013, p. 2077-2086.

Research output: Contribution to journalArticle

Bae, Sang Mun ; Kim, Jong Ho ; Chung, Seung Woo ; Byun, Youngro ; Kim, Sang Yoon ; Lee, Byung Heon ; Kim, In-San ; Park, Rang Woon. / An apoptosis-homing peptide-conjugated low molecular weight heparin-taurocholate conjugate with antitumor properties. In: Biomaterials. 2013 ; Vol. 34, No. 8. pp. 2077-2086.
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