Characterization of a specific phage-displayed Peptide binding to vasculature of human gastric cancer.
Antivascular therapy provides a promising method for anticancer therapy. But targeting to gastric cancer vessels is nonselective due in part to the lack of specific cell-surface receptors identified on target vascular cells. Herein we used in vivo screening of phage displayed peptide library to identify some peptides that bind selectively to endothelial cells of human gastric cancer rather than nonendothelial cells. After four rounds of selection, one phage was obtained with a cyclic 7-mer peptide CGNSNPKSC homing to human gastric adenocarcinoma . There was a 4.6 approximately 137.26-fold increase in the number of the selected phage in gastric cancer xenograft in comparision with control organs brain, heart, liver, spleen and kidney. Immunohistochemistry in mouse and human tissue showed that this phage peptide only bind to the endothelial cells of human gastric cancer. This peptide was observed only specific binding to HUVEC not to SGC-7901, Eca-109, LoVo and Hep-G2 by ELISA. The competitive and inhibitory result between the synthetic CGNSNPKSC peptide and the phage displaying the peptide CGNSNPKSC on HUVEC and in vivo was also confirmed its specific binding effect. This peptide may be a possible candidate for targeted drug delivery in antivascular therapy.
Zhi
Min
M
Department of Gastroenterology, The Second Hospital of Xi'an Jiaotong University, Xi'an, China.
Wu
Kai-Chun
KC
Dong
Lei
L
Hao
Zhi-Ming
ZM
Deng
Tao-Zhi
TZ
Hong
Liu
L
Liang
Shu-Hui
SH
Zhao
Peng-Tao
PT
Qiao
Tai-Dong
TD
Wang
Yu
Y
Xu
Xin
X
Fan
Da-Ming
DM
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D019151:Peptide Library; D011485:Protein Binding; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism*; D014018:Tissue Distribution
D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D019151:Peptide Library