title: A new non-muscle-invasive bladder tumor-homing peptide identified by phage display in vivo.
abstract: Bladder cancer is common and widespread, and its incidence is increasing. Many new diagnostic methods combined with state-of-the-art technology have been introduced in cystoscopy to collect real-time images of the bladder mucosa for diagnosis, but often miss inconspicuous early-stage tumors. Fluorophore-labeled peptides with high sensitivity and specificity for cancer would be a desirable tool for the detection and treatment of tiny or residual bladder tumors. Phage display and the human non-muscle-invasive bladder cancer cell line BIU-87 were used to identify a peptide. The isolated phage display peptide (CSSPIGRHC, named NYZL1) was tested in vitro for its binding specificity and affinity. Accumulation into xenograft tumors in a nude mouse model was analyzed with FITC-labeled NYZL1. NYZL1, with strong tumor‑homing ability, was identified by in vivo phage library selection in the bladder cancer model. The NYZL1 phage and synthetic FITC-labeled NYZL1 peptides bound to tumor tissues and cells, but were hardly detected in normal control organs. Notably, accumulation of FITC-NYZL1 in bladder tumor cells was time-dependent. Biodistribution studies of xenografts of BIU-87 cells showed accumulation of injected FITC-NYZL1 in the tumors, and the bound peptide could not be removed by perfusion after 24 h. The mouse model of bladder tumor showed increased fluorescence intensity in the tumor-bearing bladder in comparison with normal bladder tissues after 4-6 h. In conclusion, NYZL1 may represent a lead peptide structure applicable in the development of optical molecular imaging.
authors.affiliation: Department of Urology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Shanxi Medical University, Graduate School, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Junqian
authors.initials: J
authors.lastname: Luo
authors.affiliation: Shanxi Medical University, Graduate School, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Pang
authors.affiliation: Shanxi Medical University, Graduate School, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Sanhua
authors.initials: S
authors.lastname: Yan
authors.affiliation: Shanxi Medical University, Graduate School, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Luo
authors.affiliation: Shanxi Medical University, Graduate School, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Jiehao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Shanxi Medical University, Graduate School, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Shanxi Medical University, Graduate School, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Xixi
authors.initials: X
authors.lastname: Su
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D061505:Cell Surface Display Techniques / Q000379:methods*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis* / Q000302:isolation & purification; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000032:analysis* / Q000302:isolation & purification; D019151:Peptide Library; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology*
chemical_list: D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D009842:Oligopeptides; D019151:Peptide Library; D016650:Fluorescein-5-isothiocyanate