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Korean J Gastroenterol  <  Volume 74(1); 2019 <  Articles

Korean J Gastroenterol 2019; 74(1): 30-41  https://doi.org/10.4166/kjg.2019.74.1.30
Development of a Pancreatic Cancer Specific Binding Peptide Using Phage Display
Dong Won Lee1,2, Jae Myung Park1 ,3, Seung Mok Yang1, Moon Hwa Kwak1, Yoon Jin Roh1, In Seok Lee3 and Myung-Gyu Choi1,3
Catholic Photomedicine Research Institute1, Department of Medical Lifescience, College of Medicine, The Catholic University of Korea2, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea3, Seoul, Korea
Correspondence to: Jae Myung Park, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. Tel: +82-2-2258-6022, Fax: +82-2-2258-2089, E-mail: parkjerry@catholic.ac.kr, ORCID: https://orcid.org/0000-0002-1534-7467

Financial support: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (NRF-2017R1D1A1B03035104) and Research Fund of Seoul St. Mary's Hospital, The Catholic University of Korea.
Received: November 19, 2018; Revised: April 18, 2019; Accepted: May 6, 2019; Published online: July 25, 2019.
© The Korean Journal of Gastroenterology. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background/Aims: Pancreatic cancer has a very poor prognosis, and early diagnosis is a way to increase the survival rate of patients. The purpose of this study was to develop pancreatic cancer-specific peptides for imaging studies.
Methods: Three pancreatic cancer cell lines, MIA PaCa-2, UACC-462, and BxPC-3, and a control cell line, CCD841, were used. Biopannings were performed on MIA PaCa-2 using a phage display library. After this, the peptides were synthesized and labeled with fluorescein isothiocyanate (FITC). Immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and fluorescence- activated cell sorter (FACS) were performed to examine the specific binding. To examine its therapeutic applications, a photosensitizer, chlorin e6 (Ce6), was conjugated on the peptide and photodynamic therapy was performed. Cell survival was investigated using a [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay.
Results: After three biopannings, the phages were amplified from 1.4×104 to 3.2×105 plaque-forming units. The most strongly binding phage was selected from the ELISA and ICC results. FITC-labeled peptide, M5, in the three pancreatic cancer cell lines showed significantly higher immunofluorescence in the ICC experiments than that of CCD841. The higher binding ability to MIA PaCa-2 cells was confirmed from FACS analysis, which showed a right shift compared to CCD841. M5 bound to Ce6 showed a significantly lower cell survival rate than that of Ce6 alone in photodynamic therapy, which was observed consistently as a change in the tumor size and fluorescence intensity in MIA PaCa-2 cell-implanted animal models.
Conclusions: This study showed that the noble peptide, M5, binds specifically to the pancreatic cancer cell line, MIA PaCa-2. The M5 peptide has potential use in future optical diagnostic and therapeutic purposes.
Keywords: Bacteriophages; Pancreatic neoplasms; Peptides; Photochemotherapy

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