1-palmitoyl-2-oleoylphosphatidylcholine and Adenocarcinoma

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.

Topics: Adenocarcinoma; Cell Line, Tumor; Cell-Penetrating Peptides; Humans; Lipids; Liposomes; Nanoparticles; Oligonucleotides; Pancreatic Neoplasms; Phosphatidylcholines; Promoter Regions, Genetic; Proto-Oncogene Proteins p21(ras)