title: Prenyl Ammonium Salts--New Carriers for Gene Delivery: A B16-F10 Mouse Melanoma Model.
abstract: OBJECTIVE
  Prenyl ammonium iodides (Amino-Prenols, APs), semi-synthetic polyprenol derivatives were studied as prospective novel gene transfer agents.
  
  
  METHODS
  AP-7, -8, -11 and -15 (aminoprenols composed of 7, 8, 11 or 15 isoprene units, respectively) were examined for their capacity to form complexes with pDNA, for cytotoxicity and ability to transfect genes to cells.
  
  
  RESULTS
  All the carriers were able to complex DNA. The highest, comparable to commercial reagents, transfection efficiency was observed for AP-15. Simultaneously, AP-15 exhibited the lowest negative impact on cell viability and proliferation--considerably lower than that of commercial agents. AP-15/DOPE complexes were also efficient to introduce pDNA to cells, without much effect on cell viability. Transfection with AP-15/DOPE complexes influenced the expression of a very few among 44 tested genes involved in cellular lipid metabolism. Furthermore, complexes containing AP-15 and therapeutic plasmid, encoding the TIMP metallopeptidase inhibitor 2 (TIMP2), introduced the TIMP2 gene with high efficiency to B16-F10 melanoma cells but not to B16-F10 melanoma tumors in C57BL/6 mice, as confirmed by TIMP2 protein level determination.
  
  
  CONCLUSIONS
  Obtained results indicate that APs have a potential as non-viral vectors for cell transfection.
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.|Department of Pharmacology, National Research Institute of Mother and Child, Warsaw, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Grecka
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Statkiewicz
authors.affiliation: Department of Applied Pharmacy and Bioengineering, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gorska
authors.affiliation: Department of Immunology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Biernacka
authors.affiliation: Department of Immunology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Monika Anna
authors.initials: MA
authors.lastname: Grygorowicz
authors.affiliation: Institute of Organic Chemistry PAS, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Masnyk
authors.affiliation: Institute of Organic Chemistry PAS, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Chmielewski
authors.affiliation: Institute of Biochemistry and Biophysics PAS, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gawarecka
authors.affiliation: Institute of Biochemistry and Biophysics PAS, Warsaw, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Chojnacki
authors.affiliation: Institute of Biochemistry and Biophysics PAS, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Swiezewska
authors.affiliation: Department of Applied Pharmacy and Bioengineering, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Malecki
mesh_terms: D064751:Ammonium Compounds / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007124:Immunoenzyme Techniques; D008081:Liposomes; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009387:Neoprene / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012513:Sarcoma, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D064751:Ammonium Compounds; D004337:Drug Carriers; D008081:Liposomes; D012333:RNA, Messenger; C016077:prenyl; D004247:DNA; D009387:Neoprene