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
Externally publishedYes

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

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