title: Novel cationic polyene glycol phospholipids as DNA transfer reagents--lack of a structure-activity relationship due to uncontrolled self-assembling processes.
abstract: Cationic glycol phospholipids were synthesized introducing chromophoric, rigid polyenoic C20:5 and C30:9 chains next to saturated flexible alkyl chains of variable lengths C6-20:0. Surface properties and liposome formation of the amphiphilic compounds were determined, the properties of liposome/DNA complexes (lipoplexes) were established using three formulations (no co-lipid, DOPE as a co-lipid, or cholesterol as a co-lipid), and the microstructure of the best transfecting compounds inspected using small angle X-ray diffraction to explore details of the partially ordered structures of the systems that constitute the series. Transfection and cytotoxicity of the lipoplexes were evaluated by DNA delivery to Chinese hamster ovary (CHO-K1) cells using the cationic glycerol phospholipid 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) as a reference compound. The uncontrollable self-association of the molecules in water resulted in aggregates and liposomes of quite different sizes without a structure-property relationship. Likewise, adding DNA to the liposomes gave rise to unpredictable sized lipoplexes, which, again, transfected without a structure-activity relationship. Nevertheless, one compound among the novel lipids (C30:9 chain paired with a C20:0 chain) exhibited comparable transfection efficiency and toxicity to the control cationic lipid EPC. Thus, the presence of a rigid polyene chain in this best performing achiral glycol lipid did not have an influence on transfection compared with the chiral glycerolipid reference ethyl phosphocholine EPC with two flexible saturated C14 chains.
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
authors.forename: Christer L
authors.initials: CL
authors.lastname: Øpstad
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zeeshan
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
authors.forename: Asma
authors.initials: A
authors.lastname: Zaidi
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway. Electronic address: richard.sliwka@ntnu.no.
authors.forename: Hans-Richard
authors.initials: HR
authors.lastname: Sliwka
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
authors.forename: Vassilia
authors.initials: V
authors.lastname: Partali
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
authors.forename: David G
authors.initials: DG
authors.lastname: Nicholson
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, United States.
authors.forename: Chinmay
authors.initials: C
authors.lastname: Surve
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, United States.
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Izower
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, United States.
authors.forename: Natalia
authors.initials: N
authors.lastname: Bk
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, United States.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Lou
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, United States.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Leopold
authors.affiliation: Department of Physics, University of Stavanger, 4036 Stavanger, Norway.
authors.forename: Helge
authors.initials: H
authors.lastname: Larsen
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; Research Division, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Liberska
authors.affiliation: Research Division, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar.
authors.forename: Nada Abdul
authors.initials: NA
authors.lastname: Khalique
authors.affiliation: Research Division, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar.
authors.forename: Liji
authors.initials: L
authors.lastname: Raju
authors.affiliation: Research Division, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar.
authors.forename: Marcella
authors.initials: M
authors.lastname: Flinterman
authors.affiliation: Research Division, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar.
authors.forename: Emile
authors.initials: E
authors.lastname: Jubeli
authors.affiliation: Pre-Medical Unit, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar. Electronic address: mdp2001@qatar-med.cornell.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Pungente
mesh_terms: D000818:Animals; D016466:CHO Cells; D002412:Cations; D006224:Cricetinae; D003412:Cricetulus; D003460:Crystallization / Q000379:methods; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D006018:Glycols / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry; D008081:Liposomes / Q000138:chemical synthesis*; D011090:Polyenes / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000737:chemistry; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D006018:Glycols; D007202:Indicators and Reagents; D008081:Liposomes; D011090:Polyenes; D013501:Surface-Active Agents; D004247:DNA
keywords: Aggregation; Amphiphiles; Carotenoids; Cations; DNA; Lipids