Wheat germ agglutinin binds to the epidermal growth factor receptor of artificial Caco-2 membranes as detected by silver nanoparticle enhanced fluorescence

Pharm Res. 2003 May;20(5):833-9. doi: 10.1023/a:1023406224028.


Purpose: The purpose of this study was to identify one of the ligands that mediate carbohydrate-specific cytoadhesion and cytoinvasion of wheat germ agglutinin (WGA)-containing drug delivery systems.

Methods: The receptor-ligand studies were performed with isolated epidermal growth factor (EGF) receptors as well as biomimetic membranes prepared from Caco-2 and A-431 cells. The binding of fluorescent labeled WGA was detected by the silver nanoparticle enhanced fluorescence technique.

Results: The binding of WGA to isolated EGF receptors is saturable and the equilibrium is reached within 1 min. The interaction between WGA and isolated EGF receptors is fully inhibited by the complementary carbohydrate and at least 85% of WGA binding to artificial Caco-2 membranes is caused by protein-carbohydrate interactions involving the tetrasialo-binding motif. The integrity and the presence of EGF-receptors in artificial Caco-2 membranes as well as their WGA-binding capacity were confirmed by immunoblot detection.

Conclusions: The glycosylated extracellular domain III of the EGF receptor is involved in the WGA-Caco-2 cell interaction. Accordingly, receptor mediated endocytosis is the basic mechanism for internalization of WGA. As the EGF receptor is overexpressed in a high number of tumors but also occurs in non-malignant tissue at considerable density, WGA-mediated drug delivery opens exciting possibilities for specific binding and uptake of poorly absorbable drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / physiology
  • Caco-2 Cells
  • ErbB Receptors / analysis
  • ErbB Receptors / metabolism*
  • Fluorescence
  • Humans
  • Membranes, Artificial*
  • Nanotechnology / methods*
  • Silver / analysis
  • Silver / metabolism*
  • Wheat Germ Agglutinins / analysis
  • Wheat Germ Agglutinins / metabolism*


  • Membranes, Artificial
  • Wheat Germ Agglutinins
  • Silver
  • ErbB Receptors