title: Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles: delivery and bioactivity in pancreatic cancer cells.
abstract: KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription factor essential for KRAS transcription. It is based on the use of palmitoyl-oleyl-phosphatidylcholine (POPC) liposomes functionalized with lipid-modified G4-decoy oligonucleotides and a lipid-modified cell penetrating TAT peptide. The potency of the strategy in pancreatic cancer cells is demonstrated by cell cytometry, confocal microscopy, clonogenic and qRT-PCR assays.
authors.affiliation: Department of Medical and Biological Sciences, P. le Kolbe 4, 33100 Udine, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cogoi
authors.affiliation: Nucleic Acid Center, Institute of Physics and Chemistry, University of Southern Denmark, DK-5230 Odense M, Denmark.|PET &Cyclotron Unit, Department of Nuclear Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark.
authors.forename: U
authors.initials: U
authors.lastname: Jakobsen
authors.affiliation: Nucleic Acid Center, Institute of Physics and Chemistry, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: E B
authors.initials: EB
authors.lastname: Pedersen
authors.affiliation: Nucleic Acid Center, Institute of Physics and Chemistry, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Department of Medical and Biological Sciences, P. le Kolbe 4, 33100 Udine, Italy.
authors.forename: L E
authors.initials: LE
authors.lastname: Xodo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D057846:Cell-Penetrating Peptides; C117307:KRAS protein, human; D008055:Lipids; D008081:Liposomes; D009841:Oligonucleotides; D010713:Phosphatidylcholines; D016283:Proto-Oncogene Proteins p21(ras); C028694:1-palmitoyl-2-oleoylphosphatidylcholine