title: Polymeric Micelles of PEG-PLA Copolymer as a Carrier for Salinomycin Against Gemcitabine-Resistant Pancreatic Cancer.
abstract: OBJECTIVE
  Resistance to gemcitabine in pancreatic cancer (PC) may account for the failure of conventional treatments. Recently, salinomycin (SAL) has been identified as selective inhibitor of cancer stem cells (CSCs). In our study, we aimed to deliver SAL to gemcitabine-resistant PC by the aid of poly ethylene glycol-b-poly lactic acid (PEG-b-PLA) polymeric micelles (PMs).
  
  
  METHODS
  SAL-loaded PMs were prepared and investigated in terms of pharmaceutical properties. MTT and Annexin V/PI assays were used to study cell proliferation and apoptosis in AsPC-1 cells in response to treatment with SAL micellar formulations. Alterations in CSC phenotype, invasion strength, and mRNA expression of epithelial mesenchymal transition (EMT) markers were also determined in the treated cells. In vivo antitumor study was performed in Balb/c AsPC-1 xenograft mice.
  
  
  RESULTS
  PM formulations of SAL were prepared in suitable size and loading traits. In gemcitabine-resistant AsPC-1 cells, SAL was found to significantly increase cell mortality and apoptosis. It was also observed that SAL micellar formulations inhibited invasion and harnessed EMT in spite of induced expression of Snail. The in vivo antitumor experiment showed significant tumor eradication and the highest survival probability in mice treated with SAL PMs.
  
  
  CONCLUSIONS
  The obtained results showed the efficacy of SAL nano-formulation against PC tumor cells.
authors.affiliation: Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Daman
authors.affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Montazeri
authors.affiliation: Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Azizi
authors.affiliation: Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Faegheh
authors.initials: F
authors.lastname: Rezaie
authors.affiliation: Department of Toxicology-Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. gilani@tums.ac.ir.|Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran. gilani@tums.ac.ir.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Gilani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D041681:NIH 3T3 Cells; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011714:Pyrans / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012995:Solubility; D013499:Surface Properties; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D011714:Pyrans; D000093542:Gemcitabine; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: cancer stem cells; epithelial mesenchymal transition; pancreatic cancer; polymeric micelles; salinomycin