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A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinomas (PDACs) constitutively express the G-protein-coupled cholecystokinin B receptor (CCKBR). In this study, we identified DNA aptamers (APs) that bind to the CCKBR and describe their characterization and targeting efficacy. Using dual SELEX selection against “exposed” C...

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Autores principales: Clawson, Gary A., Abraham, Thomas, Pan, Weihua, Tang, Xiaomeng, Linton, Samuel S., McGovern, Christopher O., Loc, Welley S., Smith, Jill P., Butler, Peter J., Kester, Mark, Adair, James H., Matters, Gail L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312616/
https://www.ncbi.nlm.nih.gov/pubmed/27754762
http://dx.doi.org/10.1089/nat.2016.0621
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author Clawson, Gary A.
Abraham, Thomas
Pan, Weihua
Tang, Xiaomeng
Linton, Samuel S.
McGovern, Christopher O.
Loc, Welley S.
Smith, Jill P.
Butler, Peter J.
Kester, Mark
Adair, James H.
Matters, Gail L.
author_facet Clawson, Gary A.
Abraham, Thomas
Pan, Weihua
Tang, Xiaomeng
Linton, Samuel S.
McGovern, Christopher O.
Loc, Welley S.
Smith, Jill P.
Butler, Peter J.
Kester, Mark
Adair, James H.
Matters, Gail L.
author_sort Clawson, Gary A.
collection PubMed
description Pancreatic ductal adenocarcinomas (PDACs) constitutively express the G-protein-coupled cholecystokinin B receptor (CCKBR). In this study, we identified DNA aptamers (APs) that bind to the CCKBR and describe their characterization and targeting efficacy. Using dual SELEX selection against “exposed” CCKBR peptides and CCKBR-expressing PDAC cells, a pool of DNA APs was identified. Further downselection was based on predicted structures and properties, and we selected eight APs for initial characterizations. The APs bound specifically to the CCKBR, and we showed not only that they did not stimulate proliferation of PDAC cell lines but rather inhibited their proliferation. We chose one AP, termed AP1153, for further binding and localization studies. We found that AP1153 did not activate CCKBR signaling pathways, and three-dimensional Confocal microscopy showed that AP1153 was internalized by PDAC cells in a receptor-mediated manner. AP1153 showed a binding affinity of 15 pM. Bioconjugation of AP1153 to the surface of fluorescent NPs greatly facilitated delivery of NPs to PDAC tumors in vivo. The selectivity of this AP-targeted NP delivery system holds promise for enhanced early detection of PDAC lesions as well as improved chemotherapeutic treatments for PDAC patients.
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spelling pubmed-53126162017-03-06 A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma Clawson, Gary A. Abraham, Thomas Pan, Weihua Tang, Xiaomeng Linton, Samuel S. McGovern, Christopher O. Loc, Welley S. Smith, Jill P. Butler, Peter J. Kester, Mark Adair, James H. Matters, Gail L. Nucleic Acid Ther Original Articles Pancreatic ductal adenocarcinomas (PDACs) constitutively express the G-protein-coupled cholecystokinin B receptor (CCKBR). In this study, we identified DNA aptamers (APs) that bind to the CCKBR and describe their characterization and targeting efficacy. Using dual SELEX selection against “exposed” CCKBR peptides and CCKBR-expressing PDAC cells, a pool of DNA APs was identified. Further downselection was based on predicted structures and properties, and we selected eight APs for initial characterizations. The APs bound specifically to the CCKBR, and we showed not only that they did not stimulate proliferation of PDAC cell lines but rather inhibited their proliferation. We chose one AP, termed AP1153, for further binding and localization studies. We found that AP1153 did not activate CCKBR signaling pathways, and three-dimensional Confocal microscopy showed that AP1153 was internalized by PDAC cells in a receptor-mediated manner. AP1153 showed a binding affinity of 15 pM. Bioconjugation of AP1153 to the surface of fluorescent NPs greatly facilitated delivery of NPs to PDAC tumors in vivo. The selectivity of this AP-targeted NP delivery system holds promise for enhanced early detection of PDAC lesions as well as improved chemotherapeutic treatments for PDAC patients. Mary Ann Liebert, Inc. 2017-02-01 2017-02-01 /pmc/articles/PMC5312616/ /pubmed/27754762 http://dx.doi.org/10.1089/nat.2016.0621 Text en © Gary A. Clawson, et al., 2017; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Original Articles
Clawson, Gary A.
Abraham, Thomas
Pan, Weihua
Tang, Xiaomeng
Linton, Samuel S.
McGovern, Christopher O.
Loc, Welley S.
Smith, Jill P.
Butler, Peter J.
Kester, Mark
Adair, James H.
Matters, Gail L.
A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma
title A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma
title_full A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma
title_fullStr A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma
title_full_unstemmed A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma
title_short A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma
title_sort cholecystokinin b receptor-specific dna aptamer for targeting pancreatic ductal adenocarcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312616/
https://www.ncbi.nlm.nih.gov/pubmed/27754762
http://dx.doi.org/10.1089/nat.2016.0621
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