In vitro identification of targeting ligands of human M cells by phage display.
To improve transport of vaccine-loaded nanoparticles, the phage display technology was used to identify novel lead peptides targeting human M cells. Using an in vitro model of the human follicle-associated epithelium (FAE) which contains both Caco-2 and M cells, a T7 phage display library was screened for its ability either to bind the apical cell surface of or to undergo transcytosis across Caco-2 cells or FAE. The selection for transcytosis across both enterocytes and FAE identified three different peptide sequences (CTGKSC, PAVLG and LRVG) with high frequency. CTGKSC and LRVG sequences enhanced phage transport across M-like cells. When polymeric nanoparticles were grafted with the sequences CTGKSC and LRVG, their transport by FAE was significantly enhanced. These peptides could therefore be used to enhance the transport of vaccine-loaded nanoparticles across the intestinal mucosal barrier.
Fievez
V
V
Université Catholique de Louvain, Institut des Sciences de la Vie, Biochimie Cellulaire, Nutritionnelle & Toxicologique, Croix du Sud, 5, 1348 Louvain-La-Neuve, Belgium.
Plapied
L
L
Plaideau
C
C
Legendre
D
D
des Rieux
A
A
Pourcelle
V
V
Freichels
H
H
Jérôme
C
C
Marchand
J
J
Préat
V
V
Schneider
Y J
YJ
D000284:Administration, Oral; D017123:Bacteriophage T7; D001692:Biological Transport; D018938:Caco-2 Cells; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008024:Ligands; D053758:Nanoparticles; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D020539:Sequence Analysis, Protein; D014612:Vaccines / Q000493:pharmacokinetics*
D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D011108:Polymers; D014612:Vaccines