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

J Control Release. 2010 Jul 14;145(2):91-101. doi: 10.1016/j.jconrel.2010.03.018. Epub 2010 Mar 31.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Doxorubicin / pharmacology*
  • Female
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Peptides, Cyclic / genetics
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / physiology
  • Serum Albumin / genetics
  • Serum Albumin / metabolism
  • Serum Albumin / pharmacology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism*


  • Antibiotics, Antineoplastic
  • Peptides, Cyclic
  • Serum Albumin
  • Doxorubicin
  • Receptor, Platelet-Derived Growth Factor beta