Design and validation of a bifunctional ligand display system for receptor targeting

Chem Biol. 2004 Aug;11(8):1081-91. doi: 10.1016/j.chembiol.2004.05.019.

Abstract

Here we developed a bacteriophage display particle designed to serve as a bifunctional entity that can target tumors while delivering an agent. We engineered a chimera phage vector containing a pIII-displayed alphav integrins-targeting moiety and a pVIII-displayed streptavidin binding adaptor moiety. By using the chimeric phage particle, targeting of alphav integrins on cells in culture and tumor-related blood vessels was shown through different applications, including luminescent quantum dots localization, surface plasmon resonance-based binding detection, and an in vivo tumor model. The strategy validated here will accelerate the discovery and characterization of receptor-ligand binding events in high throughput, and cell-specific delivery of diagnostics or therapeutics to organs of choice without the need for chemical conjugation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacteriophages / genetics
  • Bacteriophages / physiology
  • Cell Line, Tumor
  • Genetic Vectors / genetics
  • Humans
  • Integrin alphaV / metabolism
  • Ligands
  • Mice
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Engineering
  • Receptors, Cell Surface / metabolism*
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / metabolism*
  • Reproducibility of Results
  • Streptavidin / metabolism
  • Streptavidin / pharmacology
  • Substrate Specificity

Substances

  • Integrin alphaV
  • Ligands
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Streptavidin