Screening and identification of a targeting peptide to hepatocarcinoma from a phage display peptide library.
Ligands specific to cell surface receptors have been heavily investigated in cancer research. Phage display technology is a powerful tool in this field and may impact clinical issues including functional diagnosis and targeted drug delivery. In this study, a hepatocellular carcinoma cell line (HepG2) and a normal hepatocyte line (L-02) were used to carry out subtractive screening in vitro with a phage display-7 peptide library. After four rounds of panning, there was an obvious enrichment for the phages specifically binding to the HepG2 cells, and the output/input ratio of phages increased about 976-fold (from 0.3x10(-7) to 292.8x10(-7)). A group of peptides capable of binding specifically to the hepatoma cells were obtained, and the affinity of these peptides to the targeting cells and tissues was studied. Through a cell-based ELISA, immunocytochemical staining, immunohistochemical staining, and immunofluorescence, the S1 phage and synthetic peptide HCBP1 (sequence FQHPSFI) were shown to bind to the tumor cell surfaces of two hepatoma cell lines and biopsy specimens, but not to normal hepatocytes, other different cancer cells, or nontumor liver tissues. In conclusion, the peptide HCBP1 may be a potential candidate for targeted drug delivery in therapy of hepatoma cancer.
Zhang
Binghua
B
Department of Pathogenic Microbiology, Xinjiang Medical University, Urumqi, Xinjiang, PR China. junzidangziqiang@yahoo.com
Zhang
Yanqiong
Y
Wang
Jiwei
J
Zhang
Yangde
Y
Chen
Jiji
J
Pan
Yifeng
Y
Ren
Lifeng
L
Hu
Zhiyuan
Z
Zhao
Jingfeng
J
Liao
Mingmei
M
Wang
Shunwei
S
D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002999:Clone Cells; D005786:Gene Expression Regulation; D006367:HeLa Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000032:analysis* / Q000737:chemistry; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D000418:Albumins; D019151:Peptide Library; D010455:Peptides; D012333:RNA, Messenger