10071 Background: Bladder cancer is one of the most common tumors of genitourinary tract. Selective delivery of drugs to tumor tissues is important for effective tumor therapy. Here we identified a peptide targeting bladder tumor cells using phage display. Methods: Phage peptide library containing CX7C (C-cysteine and X-any amino acid residue) was based on T7 415–1b phage vector (Novagen). Tumor xenografts were prepared by subcutaneously injecting BALB/c Nu/nu female nude mice with HT-1376 bladder tumor cells. For a carcinogen-induced tumor model, Fischer 344 female rats were supplied ad libitum with tap water containing 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 8 weeks. Results: A phage library containing CX7C random peptides was screened for selective binding to cells from human bladder tumor xenografts. Selected phage clones were individually evaluated for binding to cultured bladder tumor cells and for binding to cells from human tumor tissues of six patients. The peptide displayed by the most promising clone was synthesized and designated as Bld-1. Fluorescein-conjugated Bld-1 peptide showed selective binding to frozen sections of human bladder tumor tissues of three patients. In vivo tumor targeting was examined in a carcinogen-induced rat tumor model (n=20). When the fluorescent peptide was introduced into the bladder lumen, it selectively bound to tumor epithelium. Next, when the fluorescent peptide was intravenously injected into the tail vein, it homed to the bladder tumor, but was not detectable in normal bladder and control organs such as lung. Moreover, the fluorescent peptide bound to cells from urinary specimens of tumor patients (n=10), whereas little binding was observed in cells from healthy individuals (n=3). Conclusions: The Bld-1 peptide may be useful for targeting bladder tumor cells in vivo and in the urine. No significant financial relationships to disclose.
A new non-muscle-invasive bladder tumor-homing peptide identified by phage display in vivo
