Peptide-mediated transcytosis of phage display vectors in MDCK cells

Biochem Biophys Res Commun. 2000 Sep 16;276(1):251-7. doi: 10.1006/bbrc.2000.3358.

Abstract

Delivery of therapeutic macromolecules and gene vectors to certain tissues is hampered by endothelial or epithelial barriers. We show here that the transport of phage particles across epithelial cells can be facilitated by peptide ligands selected from a phage library of random peptides. Using MDCK cells, we identified a polycationic peptide sequence, RYRGDLGRR, containing a putative integrin-binding (RGD) motif that enhanced basal-to-apical transcytosis of peptide-bearing phage 1000- to 10,000-fold compared with phage with no peptide insert. Both the synthetic peptide RYRGDLGRR and the integrin-binding peptide GRGDSP inhibited phage transcytosis suggesting the involvement of integrins. Confocal immunofluorescence microscopy showed that following internalization at the basal cell surface, phage particles were delivered to the apical cytoplasm and released at the apical cell surface. These data suggest the feasibility of using short peptides for targeting transcytotic pathways and facilitating delivery of macromolecules across cellular barriers.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Cell Line
  • Dogs
  • Drug Carriers*
  • Drug Delivery Systems*
  • Genetic Vectors
  • Integrins*
  • Ligands
  • Molecular Sequence Data
  • Peptide Library
  • Peptides* / genetics

Substances

  • Drug Carriers
  • Integrins
  • Ligands
  • Peptide Library
  • Peptides