title: Optimizing cationic and neutral lipids for efficient gene delivery at high serum content.
abstract: BACKGROUND
  Cationic liposome (CL)-DNA complexes are promising gene delivery vectors with potential application in gene therapy. A key challenge in creating CL-DNA complexes for application is that their transfection efficiency (TE) is adversely affected by serum. In particular, little is known about the effects of a high serum content on TE, even though this may provide design guidelines for application in vivo.
  
  
  METHODS
  We prepared CL-DNA complexes in which we varied the neutral lipid [1,2-dioleoyl-sn-glycerophosphatidylcholine, glycerol-monooleate (GMO), cholesterol], the headgroup charge and chemical structure of the cationic lipid, and the ratio of neutral to cationic lipid; we then measured the TE of these complexes as a function of serum content and assessed their cytotoxicity. We tested selected formulations in two human cancer cell lines (M21/melanoma and PC-3/prostate cancer).
  
  
  RESULTS
  In the absence of serum, all CL-DNA complexes of custom-synthesized multivalent lipids show high TE. Certain combinations of multivalent lipids and neutral lipids, such as MVL5(5+)/GMO-DNA complexes or complexes based on the dendritic-headgroup lipid TMVLG3(8+) exhibited high TE both in the absence and presence of serum. Although their TE still dropped to a small extent in the presence of serum, it reached or surpassed that of benchmark commercial transfection reagents, particularly at a high serum content.
  
  
  CONCLUSIONS
  Two-component vectors (one multivalent cationic lipid and one neutral lipid) can rival or surpass benchmark reagents at low and high serum contents (up to 50%, v/v). We propose guidelines for optimizing the serum resistance of CL-DNA complexes based on a given cationic lipid.
authors.affiliation: Department of Materials, Department of Physics, and Molecular, Cellular & Developmental Biology Department, University of California at Santa Barbara, California 93106, USA.|Institute of Physics, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chan
authors.affiliation: Department of Materials, Department of Physics, and Molecular, Cellular & Developmental Biology Department, University of California at Santa Barbara, California 93106, USA.
authors.forename: Kai K
authors.initials: KK
authors.lastname: Ewert
authors.affiliation: Department of Materials, Department of Physics, and Molecular, Cellular & Developmental Biology Department, University of California at Santa Barbara, California 93106, USA.
authors.forename: Ramsey N
authors.initials: RN
authors.lastname: Majzoub
authors.affiliation: Institute of Physics, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yeu-Kuang
authors.initials: YK
authors.lastname: Hwu
authors.affiliation: National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.|Department of Electrophysics, National Chiao-Tung University, Hsinchu 30010, Taiwan.
authors.forename: Keng S
authors.initials: KS
authors.lastname: Liang
authors.affiliation: Department of Materials, Department of Physics, and Molecular, Cellular & Developmental Biology Department, University of California at Santa Barbara, California 93106, USA.
authors.forename: Cecília
authors.initials: C
authors.lastname: Leal
authors.affiliation: Department of Materials, Department of Physics, and Molecular, Cellular & Developmental Biology Department, University of California at Santa Barbara, California 93106, USA.
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Safinya
mesh_terms: D001549:Benzamides / Q000737:chemistry; D002412:Cations / Q000737:chemistry*; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D010957:Plasmids / Q000235:genetics; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D044967:Serum / Q000737:chemistry; D013096:Spermine / Q000031:analogs & derivatives / Q000737:chemistry; D014162:Transfection
chemical_list: D001549:Benzamides; D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D008081:Liposomes; C468789:N1-(2-(1-((3-aminopropyl)amino)-4-(di-(3-aminopropyl)amino)butylcarboxamido)ethyl)-3,4-di-(oleyloxy)benzamide; D000644:Quaternary Ammonium Compounds; D013096:Spermine; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: cationic liposomes; gene delivery; glycerol monooleate; multivalent cationic lipid; serum
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