title: Polymeric micelles for MCL-1 gene silencing in breast tumors following systemic administration.
abstract: To develop delivery systems for efficient siRNA delivery to breast cancer.
  
  
  
  Poly(ethylene oxide)-block-poly(ϵ-caprolactone-grafted-spermine) (PEO-b-P(CL-g-SP)) micelles were modified with cholesterol group in their core and with RGD4C peptide on their shell. Transfection efficiency of complexed MCL-1 siRNA in MDA-MB-435 was investigated, in vitro and in vivo following intratumoral and intravenous injection.
  
  
  
  Cholesteryl modification of the core significantly increased the transfection efficiency of PEO-b-P(CL-g-SP)-complexed siRNA, in vitro, but not following intratumoral or intravenous administration, in vivo. Instead, RGD4C modification of the micellar shell enhanced transfection efficiency of complexed MCL-1 siRNA in tumor upon intravenous administration.
  
  
  
  RGD4C-PEO-b-P(CL-g-SP) micelles, without or with cholesterol modification, can provide efficient delivery of siRNA to breast tumors following systemic administration.
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.
authors.forename: Shyam M
authors.initials: SM
authors.lastname: Garg
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.
authors.forename: Arash
authors.initials: A
authors.lastname: Falamarzian
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Vakili
authors.affiliation: Department of Biomedical & Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA 92618, USA.
authors.forename: Hamidreza M
authors.initials: HM
authors.lastname: Aliabadi
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.|Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, T6G 2V4, Canada.
authors.forename: Hasan
authors.initials: H
authors.lastname: Uludağ
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.|Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, T6G 2V4, Canada.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002208:Caproates / Q000737:chemistry*; D005260:Female; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D008819:Mice, Nude; D008823:Micelles; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D000067492:RNAi Therapeutics / Q000379:methods*; D013096:Spermine / Q000031:analogs & derivatives; D014162:Transfection / Q000379:methods
chemical_list: D002208:Caproates; D007783:Lactones; C579095:MCL1 protein, human; D008823:Micelles; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D034741:RNA, Small Interfering; D013096:Spermine; D011092:Polyethylene Glycols; C121056:caprolactone
keywords: MCL-1; MDA-MB-435; PEO-b-PCL; RGD4C; cancer; cholesterol; polymeric micelles; siRNA delivery; spermine