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Nucleic Acid Ther. 2017 Feb;27(1):23-35. doi: 10.1089/nat.2016.0621. Epub 2016 Oct 18.

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

Author information

1
1 Department of Pathology, Gittlen Cancer Research Laboratories, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
2
2 Department of Neural and Behavioral Sciences and the Microscopy Imaging Facility, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
3
3 Department of Chemistry, Pennsylvania State University , University Park, Pennsylvania.
4
4 Department of Materials Science and Engineering, Pennsylvania State University , University Park, Pennsylvania.
5
5 Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
6
6 Department of Medicine, Georgetown University , Washington, District of Columbia.
7
7 Department of Bioengineering, Pennsylvania State University , University Park, Pennsylvania.
8
8 Department of Pharmacology, University of Virginia , Charlottesville, Virginia.

Abstract

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.

KEYWORDS:

DNA aptamer; pancreatic cancer; targeted nanoparticles; tumor imaging

PMID:
27754762
PMCID:
PMC5312616
DOI:
10.1089/nat.2016.0621
[Indexed for MEDLINE]
Free PMC Article

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