Targeting the gut barrier: identification of a homing peptide sequence for delivery into the injured intestinal epithelial cell.
BACKGROUND
Severe injury results in intestinal barrier dysfunction that may be responsible for significant morbidity and mortality. We postulated that mining a peptide library that was displayed on phage would identify peptide sequences that bind and internalize into the gut epithelium following injury.


METHODS
We utilized a severe full thickness burn in mice as a model of severe injury. Candidate peptides were identified by screening 10(12) phage displaying unique peptide sequences. In vivo assessment was performed by injecting targeted phage into the lumen of a segment of distal ileum following burn injury, then analyzed for uptake of peptide sequence using quantitative polymerase chain reaction (PCR), DNA sequencing, and confocal microscopy of the peptide bound to quantum dots (Qdots).


RESULTS
Phage screening identified the peptide sequence T18 (LTHPQDSPPASA) as an optimal candidate for in vivo testing. PCR of intestinal cells following injury showed a higher level of T18 sequence when compared to untargeted phage. Confocal microscopy of the peptide sequence bound to Qdots showed internalization into gut mucosa following injury.


CONCLUSIONS
We have identified a peptide sequence that targets the injured intestinal epithelium and may allow for the development of targeted therapies to attenuate inflammation, or other pathologic conditions of the small bowel.
Costantini
Todd W
TW
Division of Trauma, Surgical Critical Care, and Burns, Department of Surgery, University of California-San Diego School of Medicine, San Diego, CA 92103-8896, USA.
Putnam
James G
JG
Sawada
Ritsuko
R
Baird
Andrew
A
Loomis
William H
WH
Eliceiri
Brian P
BP
Bansal
Vishal
V
Coimbra
Raul
R
D000595:Amino Acid Sequence; D000818:Animals; D002056:Burns / Q000378:metabolism*; D034201:Computers, Handheld; D007082:Ileum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D019151:Peptide Library; D045663:Quantum Dots
D019151:Peptide Library