Multivalent display and receptor-mediated endocytosis of transferrin on virus-like particles

Deboshri Banerjee, Allen P. Liu, Neil R. Voss, Sandra L. Schmid, M. G. Finn

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

The structurally regular and stable self-assembled capsids derived from viruses can be used as scaffolds for the display of multiple copies of cell- and tissue-targeting molecules and therapeutic agents in a convenient and well-defined manner. The human iron-transfer protein transferrin, a high affinity ligand for receptors upregulated in a variety of cancers, has been arrayed on the exterior surface of the protein capsid of bacteriophage Qβ. Selective oxidation of the sialic acid residues on the glycan chains of transferrin was followed by introduction of a terminal alkyne functionality through an oxime linkage. Attachment of the protein to azide-functionalized Qβ capsid particles in an orientation allowing access to the receptor binding site was accomplished by the CuI-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Transferrin conjugation to Qβ particles allowed specific recognition by transferrin receptors and cellular internalization through clathrin-mediated endocytosis, as determined by fluorescence microscopy on cells expressing GFP-labeled clathrin light chains. By testing Qβ particles bearing different numbers of transferrin molecules, it was demonstrated that cellular uptake was proportional to ligand density, but that internalization was inhibited by equivalent concentrations of free transferrin. These results suggest that cell targeting with transferrin can be improved by local concentration (avidity) effects.

Original languageEnglish (US)
Pages (from-to)1273-1279
Number of pages7
JournalChemBioChem
Volume11
Issue number9
DOIs
StatePublished - Jun 14 2010

Keywords

  • Click chemistry
  • Polyvalency
  • Receptor-mediated endocytosis
  • Transferrin
  • Viruses

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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    Banerjee, D., Liu, A. P., Voss, N. R., Schmid, S. L., & Finn, M. G. (2010). Multivalent display and receptor-mediated endocytosis of transferrin on virus-like particles. ChemBioChem, 11(9), 1273-1279. https://doi.org/10.1002/cbic.201000125