Selection of pancreatic cancer cell-binding landscape phages and their use in development of anticancer nanomedicines

Protein Eng Des Sel. 2014 Jul;27(7):235-43. doi: 10.1093/protein/gzu020. Epub 2014 Jun 4.


It is hypothesized that the use of targeted drug delivery systems can significantly improve the therapeutic index of small molecule chemotherapies by enhancing accumulation of the drugs at the site of disease. Phage display offers a high-throughput approach for selection of the targeting ligands. We have successfully isolated phage fusion proteins selective and specific for PANC-1 pancreatic cancer cells. Doxorubicin liposomes (Lipodox) modified with tumor-specific phage fusion proteins enhanced doxorubicin uptake specifically in PANC-1 cells as compared with unmodified Lipodox and also compared with normal breast epithelial cells. Phage protein-targeted Lipodox substantially increased the concentration of doxorubicin in the nuclei of PANC-1 cells in spite of P-glycoprotein-mediated drug efflux. The in vitro cytotoxic activity obtained with pancreatic cell-targeted Lipodox was greater than that of unmodified Lipodox. We present a novel and straightforward method for preparing pancreatic tumor-targeted nanomedicines by anchoring pancreatic cancer-specific phage proteins within the liposome bilayer.

Keywords: drug delivery; landscape phage; liposome; major coat protein pVIII; pancreatic cancer; phage display.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Amino Acid Sequence
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Doxorubicin / analogs & derivatives
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Delivery Systems / methods*
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • Molecular Sequence Data
  • Nanomedicine / methods*
  • Pancreatic Neoplasms / pathology*
  • Peptide Library*
  • Polyethylene Glycols / metabolism
  • Polyethylene Glycols / pharmacology
  • Protein Transport
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism*
  • Substrate Specificity


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Peptide Library
  • Recombinant Fusion Proteins
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin