A novel approach to deliver anticancer drugs to key cell types in tumors using a PDGF receptor-binding cyclic peptide containing carrier

Jai Prakash*, Edwin de Jong, Eduard Post, Annette S. H. Gouw, Leonie Beljaars, Klaas Poelstra

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

48 Citations (Scopus)

Abstract

Tumor stromal cells have been recently recognized to contribute to tumor growth. Therefore, we hypothesized that delivery of anticancer drugs to these cells in addition to the tumor cells might treat cancer more effectively. Stromal cells abundantly expressed Platelet-Derived Growth Factor Receptor-beta (PDGFR-beta) in different human tumors as shown with immunohistochemistry. To achieve targeting through PDGFR-beta, we developed a carrier by modifying albumin with a PDGFR-beta recognizing cyclic peptide (pPB-HSA). pPB-HSA specifically bound to PDGFR-beta-expressing 3T3 fibroblasts, C26 and A2780 cancer cells in vitro. Subsequently, doxorubicin was conjugated to pPB-HSA through an acid-sensitive hydrazone linkage. In vitro, Dox-HSA-pPB was taken up by fibroblasts and tumor cells and a short exposure of the conjugate induced cell death in these cells. In vivo, the conjugate rapidly accumulated into PDGFR-beta expressing cells in C26 tumors. Treatment with Dox-HSA-pPB significantly reduced the C26 tumor growth in mice while free doxorubicin treated mice had lower response to the therapy. Furthermore, in contrast to free doxorubicin the conjugate did not induce loss in body weight. In conclusion, the present study reveals a novel approach to target key cell types in tumors through PDGFR-beta, which can be applied to enhance the therapeutic efficacy of anticancer drugs. (C) 2010 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)91-101
Number of pages11
JournalJournal of Controlled Release
Volume145
Issue number2
DOIs
Publication statusPublished - 14-Jul-2010

Keywords

  • PDGF receptor
  • Cyclic peptide
  • Intracellular delivery
  • Stromal targeting
  • GROWTH-FACTOR RECEPTOR
  • ALBUMIN-BINDING
  • IN-VIVO
  • CANCER
  • THERAPEUTICS
  • VASCULATURE
  • NANOMEDICINES
  • DOXORUBICIN
  • PRODRUGS
  • DISEASE

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