title: Selection of pancreatic cancer cell-binding landscape phages and their use in development of anticancer nanomedicines.
abstract: It is hypothesized that the use of targeted drug delivery systems can significantly improve the therapeutic index of small molecule chemotherapies by enhancing accumulation of the drugs at the site of disease. Phage display offers a high-throughput approach for selection of the targeting ligands. We have successfully isolated phage fusion proteins selective and specific for PANC-1 pancreatic cancer cells. Doxorubicin liposomes (Lipodox) modified with tumor-specific phage fusion proteins enhanced doxorubicin uptake specifically in PANC-1 cells as compared with unmodified Lipodox and also compared with normal breast epithelial cells. Phage protein-targeted Lipodox substantially increased the concentration of doxorubicin in the nuclei of PANC-1 cells in spite of P-glycoprotein-mediated drug efflux. The in vitro cytotoxic activity obtained with pancreatic cell-targeted Lipodox was greater than that of unmodified Lipodox. We present a novel and straightforward method for preparing pancreatic tumor-targeted nanomedicines by anchoring pancreatic cancer-specific phage proteins within the liposome bilayer.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL 36849, USA Current address: College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Bedi
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL 36849, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Gillespie
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL 36849, USA petreva@auburn.edu.
authors.forename: Valery A
authors.initials: VA
authors.lastname: Petrenko
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D050997:Nanomedicine / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D019151:Peptide Library; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D019151:Peptide Library; D011993:Recombinant Fusion Proteins; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: drug delivery; landscape phage; liposome; major coat protein pVIII; pancreatic cancer; phage display