A new non-muscle-invasive bladder tumor-homing peptide identified by phage display in vivo

Yang,Xiaofeng; Zhang,Fan; Luo,Junqian; Pang,Jianzhi; Yan,Sanhua; Luo,Fang; Liu,Jiehao; Wang,Wei; Cui,Yongping; Su,Xixi

doi:10.3892/or.2016.4829

A new non-muscle-invasive bladder tumor-homing peptide identified by phage display in vivo

Authors:
- Xiaofeng Yang
- Fan Zhang
- Junqian Luo
- Jianzhi Pang
- Sanhua Yan
- Fang Luo
- Jiehao Liu
- Wei Wang
- Yongping Cui
- Xixi Su
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Affiliations: Department of Urology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Shanxi Medical University, Graduate School, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
Published online on: May 23, 2016 https://doi.org/10.3892/or.2016.4829
Pages: 79-89
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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