title: A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma.
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.
authors.affiliation: 1 Department of Pathology, Gittlen Cancer Research Laboratories, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Clawson
authors.affiliation: 2 Department of Neural and Behavioral Sciences and the Microscopy Imaging Facility, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
authors.forename: Thomas
authors.initials: T
authors.lastname: Abraham
authors.affiliation: 1 Department of Pathology, Gittlen Cancer Research Laboratories, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
authors.forename: Weihua
authors.initials: W
authors.lastname: Pan
authors.affiliation: 3 Department of Chemistry, Pennsylvania State University , University Park, Pennsylvania.|4 Department of Materials Science and Engineering, Pennsylvania State University , University Park, Pennsylvania.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Tang
authors.affiliation: 5 Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Linton
authors.affiliation: 5 Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
authors.forename: Christopher O
authors.initials: CO
authors.lastname: McGovern
authors.affiliation: 3 Department of Chemistry, Pennsylvania State University , University Park, Pennsylvania.|4 Department of Materials Science and Engineering, Pennsylvania State University , University Park, Pennsylvania.
authors.forename: Welley S
authors.initials: WS
authors.lastname: Loc
authors.affiliation: 6 Department of Medicine, Georgetown University , Washington, District of Columbia.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Smith
authors.affiliation: 7 Department of Bioengineering, Pennsylvania State University , University Park, Pennsylvania.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Butler
authors.affiliation: 8 Department of Pharmacology, University of Virginia , Charlottesville, Virginia.
authors.forename: Mark
authors.initials: M
authors.lastname: Kester
authors.affiliation: 4 Department of Materials Science and Engineering, Pennsylvania State University , University Park, Pennsylvania.
authors.forename: James H
authors.initials: JH
authors.lastname: Adair
authors.affiliation: 5 Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
authors.forename: Gail L
authors.initials: GL
authors.lastname: Matters
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D019556:COS Cells; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D016503:Drug Delivery Systems; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D058726:Nanoconjugates / Q000008:administration & dosage* / Q000737:chemistry; D061848:Optical Imaging; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D043887:Receptor, Cholecystokinin B / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D000068936:Theranostic Nanomedicine; D023041:Xenograft Model Antitumor Assays
chemical_list: D052157:Aptamers, Nucleotide; D058726:Nanoconjugates; D043887:Receptor, Cholecystokinin B
keywords: DNA aptamer; pancreatic cancer; targeted nanoparticles; tumor imaging