title: Polyene-based cationic lipids as visually traceable siRNA transfer reagents.
abstract: Cationic lipids are promising non-viral vectors for the cellular delivery of nucleic acids. Important considerations for the development of new delivery vectors are enhanced uptake efficiency, low toxicity and traceability. Traceable gene transfer systems however typically require the inclusion of a labeled excipient, and highly sensitive imaging instrumentation to detect the presence of the label. Recently, we reported the synthesis and characterization of colored, polyene cationic phospholipidoids composed of a rigid, polyenoic acid of predetermined dimension (C20:5 and C30:9) paired with flexible saturated alkyl chains of varying lengths (12:0, 14:0, 16:0, 18:0, 20:0 carbons). Herein, the potential of these cationic phospholipids as siRNA carriers was evaluated through standard liposomal formulations in combination with a neutral helper lipid DOPE. The polyene-based lipids were compared with a standard cationic lipid for siRNA-delivery into luciferase expressing HR5-CL11 cells. Within the series of lipids screened, knockdown results indicated that polyene cationic phospholipids paired with longer saturated alkyl chains are more effective as gene transfer agents, and perform comparably with the commercial lipid EPC. Furthermore, the chromophore associated with the polyene chain allowed tracking of the siRNA delivery using direct observation. The polyene lipoplexes were tracked on both a macroscopic and microscopic level either as a single-component or as a multi-component lipoplex formulation. When combined with a reference EPC, effective knockdown and tracking abilities were combined in a single preparation.
authors.affiliation: Université Paris-Sud, EA 401, IFR 141, Faculté de pharmacie, Châtenay Malabry, France. Electronic address: emile.jubeli@u-psud.fr.
authors.forename: Emile
authors.initials: E
authors.lastname: Jubeli
authors.affiliation: Research Division, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors.forename: Liji
authors.initials: L
authors.lastname: Raju
authors.affiliation: Research Division, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors.forename: Nada Abdul
authors.initials: NA
authors.lastname: Khalique
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Bk
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Zegel
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA.
authors.forename: Agape
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Lou
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Christer L
authors.initials: CL
authors.lastname: Øpstad
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zeeshan
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Hans-Richard
authors.initials: HR
authors.lastname: Sliwka
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Vassilia
authors.initials: V
authors.lastname: Partali
authors.affiliation: Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Leopold
authors.affiliation: Premedical Unit, Weill Cornell Medical College in Qatar, Doha, Qatar. Electronic address: mdp2001@qatar-med.cornell.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Pungente
mesh_terms: D002412:Cations / Q000737:chemistry*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008156:Luciferases / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011090:Polyenes / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics; D014162:Transfection / Q000379:methods
chemical_list: D002412:Cations; D007202:Indicators and Reagents; D008055:Lipids; D008081:Liposomes; D010743:Phospholipids; D011090:Polyenes; D034741:RNA, Small Interfering; D008156:Luciferases
keywords: Carotenoids; Cationic liposomes; Gene delivery; Knockdown; Polyene-based lipids; Traceable; siRNA