Skip to main content
SpringerLink
Log in

Cationic Lipids: Molecular Structure/Transfection Activity Relationships and Interactions with Biomembranes

  • Chapter
  • First Online:
Nucleic Acid Transfection

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 296))

Abstract

Synthetic cationic lipids, which form complexes (lipoplexes) with polyanionic DNA, are presently the most widely used constituents of nonviral gene carriers. A large number of cationic amphiphiles have been synthesized and tested in transfection studies. However, due to the complexity of the transfection pathway, no general schemes have emerged for correlating the cationic lipid chemistry with their transfection efficacy and the approaches for optimizing their molecular structures are still largely empirical. Here we summarize data on the relationships between transfection activity and cationic lipid molecular structure and demonstrate that the transfection activity depends in a systematic way on the lipid hydrocarbon chain structure. A number of examples, including a large series of cationic phosphatidylcholine derivatives, show that optimum transfection is displayed by lipids with chain length of ∼14 carbon atoms and that the transfection efficiency strongly increases with increase of chain unsaturation, specifically upon replacement of saturated with monounsaturated chains.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Venter JC, Adams MD, Myers EW et al (2001) The sequence of the human genome. Science 291:1304–1351

    Article  PubMed  CAS  Google Scholar 

  2. Flotte TR (2007) Gene therapy: the first two decades and the current state-of-the-art. J Cell Physiol 213:301–305

    Article  PubMed  CAS  Google Scholar 

  3. Giacca M (2007) Virus-mediated gene transfer to induce therapeutic angiogenesis: where do we stand? Int J Nanomedicine 2:527–540

    PubMed  CAS  Google Scholar 

  4. Hendrie PC, Russell DW (2005) Gene targeting with viral vectors. Mol Ther 12:9–17

    Article  PubMed  CAS  Google Scholar 

  5. Felgner PL, Ringold GM (1989) Cationic liposome-mediated transfection. Nature 337:387–388

    Article  PubMed  CAS  Google Scholar 

  6. Gao X, Huang L (1991) A novel cationic liposome reagent for efficient transfection of mammalian cells. Biochem Biophys Res Commun 179:280–285

    Article  PubMed  CAS  Google Scholar 

  7. Leventis R, Silvius JR (1990) Interactions of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. Biochim Biophys Acta 1023:124–132

    Article  PubMed  CAS  Google Scholar 

  8. Gaucheron J, Wong T, Wong EF et al (2002) Synthesis and properties of novel tetraalkyl cationic lipids. Bioconjug Chem 13:671–675

    Article  PubMed  CAS  Google Scholar 

  9. Ghosh YK, Visweswariah SS, Bhattacharya S (2002) Advantage of the ether linkage between the positive charge and the cholesteryl skeleton in cholesterol-based amphiphiles as vectors for gene delivery. Bioconjug Chem 13:378–384

    Article  PubMed  CAS  Google Scholar 

  10. Jaaskelainen I, Sternberg B, Monkkonen J et al (1998) Physicochemical and morphological properties of complexes made of cationic liposomes and oligonucleotides. Int J Pharm 167:191–203

    Article  CAS  Google Scholar 

  11. Lobo BA, Vetro JA, Suich DM et al (2003) Structure/function analysis of peptoid/lipitoid: DNA complexes. J Pharm Sci 92:1905–1918

    Article  PubMed  CAS  Google Scholar 

  12. Niculescu-Duvaz D, Heyes J, Springer CJ (2003) Structure–activity relationship in cationic lipid mediated gene transfection. Curr Med Chem 10:1233–1261

    Article  PubMed  CAS  Google Scholar 

  13. Song YK, Liu F, Chu SY et al (1997) Characterization of cationic liposome-mediated gene transfer in vivo by intravenous administration. Human Gene Ther 8:1585–1594

    Article  CAS  Google Scholar 

  14. Subramanian M, Holopainen JM, Paukku T et al (2000) Characterisation of three novel cationic lipids as liposomal complexes with DNA. Biochim Biophys Acta-Biomembranes 1466:289–305

    Article  CAS  Google Scholar 

  15. Pinnaduwage P, Schmitt L, Huang L (1989) Use of a quaternary ammonium detergent in liposome mediated DNA transfection of mouse L-cells. Biochim Biophys Acta 985:33–37

    Article  PubMed  CAS  Google Scholar 

  16. MacDonald RC, Ashley GW, Shida MM et al (1999) Physical and biological properties of cationic triesters of phosphatidylcholine. Biophys J 77:2612–2629

    Article  PubMed  CAS  Google Scholar 

  17. MacDonald RC, Rakhmanova VA, Choi KL et al (1999) O-Ethylphosphatidylcholine: a metabolizable cationic phospholipid which is a serum-compatible DNA transfection agent. J Pharm Sci 88:896–904

    Article  PubMed  CAS  Google Scholar 

  18. Solodin I, Brown CS, Heath TD (1996) Synthesis of phosphotriester cationic phospholipids. Cationic lipids 2. Synlett 5:457–458

    Article  Google Scholar 

  19. Koynova R, MacDonald RC (2003) Cationic O-ethylphosphatidylcholines and their lipoplexes: phase behavior aspects, structural organization and morphology. Biochim Biophys Acta-Biomembranes 1613:39–48

    Article  CAS  Google Scholar 

  20. Koynova R, Wang L, MacDonald RC (2008) Cationic phospholipids forming cubic phases: lipoplex structure and transfection efficiency. Mol Pharm 5:739–744

    Article  PubMed  CAS  Google Scholar 

  21. Wang L, Koynova R, Parikh H et al (2006) Transfection activity of binary mixtures of cationic O-substituted phosphatidylcholine derivatives: the hydrophobic core strongly modulates their physical properties and DNA delivery efficacy. Biophys J 91:3692–3706

    Article  PubMed  CAS  Google Scholar 

  22. Lewis RNAH, Winter I, Kriechbaum M et al (2001) Studies of the structure and organization of cationic lipid bilayer membranes: calorimetric, spectroscopic, and x-ray diffraction studies of linear saturated P-O-ethyl phosphatidylcholines. Biophys J 80:1329–1342

    Article  PubMed  CAS  Google Scholar 

  23. Winter I, Pabst G, Rappolt M et al (2001) Refined structure of 1, 2-diacyl-P-O-ethylphosphatidylcholine bilayer membranes. Chem Phys Lipids 112:137–150

    Article  PubMed  CAS  Google Scholar 

  24. Rakhmanova VA, McIntosh TJ, MacDonald RC (2000) Effects of dioleoylphosphatidylethanolamine on the activity and structure of O-alkyl phosphatidylcholine-DNA transfection complexes. Cell Mol Biol Lett 5:51–65

    CAS  Google Scholar 

  25. Rosenzweig HS, Rakhmanova VA, McIntosh TJ et al (2000) O-Alkyl dioleoylphosphatidylcholinium compounds: the effect of varying alkyl chain length on their physical properties and in vitro DNA transfection activity. Bioconjug Chem 11:306–313

    Article  PubMed  CAS  Google Scholar 

  26. Koynova R, Tenchov B, Wang L et al (2009) Hydrophobic moiety of cationic lipids strongly modulates their transfection activity. Mol Pharm 6:951–958

    Article  PubMed  CAS  Google Scholar 

  27. Heyes JA, Niculescu-Duvaz D, Cooper RG et al (2002) Synthesis of novel cationic lipids: effect of structural modification on the efficiency of gene transfer. J Med Chem 45:99–114

    Article  PubMed  CAS  Google Scholar 

  28. Karmali PP, Chaudhuri A (2007) Cationic liposomes as non-viral carriers of gene medicines: resolved issues, open questions, and future promises. Med Res Rev 27:696–722

    Article  PubMed  CAS  Google Scholar 

  29. Karmali PP, Kumar VV, Chaudhuri A (2004) Design, syntheses and in vitro gene delivery efficacies of novel mono-, di- and trilysinated cationic lipids: a structure-activity investigation. J Med Chem 47:2123–2132

    Article  PubMed  CAS  Google Scholar 

  30. Floch V, Loisel S, Guenin E et al (2000) Cation substitution in cationic phosphonolipids: a new concept to improve transfection activity and decrease cellular toxicity. J Med Chem 43:4617–4628

    Article  PubMed  CAS  Google Scholar 

  31. Behr JP, Demeneix B, Loeffler JP et al (1989) Efficient gene-transfer into mammalian primary endocrine-cells with lipopolyamine-coated DNA. Proc Natl Acad Sci USA 86:6982–6986

    Article  PubMed  CAS  Google Scholar 

  32. Ferrari ME, Nguyen CM, Zelphati O et al (1998) Analytical methods for the characterization of cationic lipid nucleic acid complexes. Hum Gene Ther 9:341–351

    Article  PubMed  CAS  Google Scholar 

  33. de Lima MCP, Neves S, Filipe A et al (2003) Cationic liposomes for gene delivery: from biophysics to biological applications. Curr Med Chem 10:1221–1231

    Article  Google Scholar 

  34. Wheeler CJ, Felgner PL, Tsai YJ et al (1996) A novel cationic lipid greatly enhances plasmid DNA delivery and expression in mouse lung. Proc Natl Acad Sci USA 93:11454–11459

    Article  PubMed  CAS  Google Scholar 

  35. Felgner JH, Kumar R, Sridhar CN et al (1994) Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations. J Biol Chem 269:2550–2561

    PubMed  CAS  Google Scholar 

  36. Lee ER, Marshall J, Siegel CS et al (1996) Detailed analysis of structures and formulations of cationic lipids for efficient gene transfer to the lung. Hum Gene Ther 7:1701–1717

    Article  PubMed  CAS  Google Scholar 

  37. Kearns MD, Donkor AM, Savva M (2008) Structure-transfection activity studies of nove cationic cholesterol-based amphiphiles. Mol Pharm 5:128–139

    Article  PubMed  CAS  Google Scholar 

  38. Bajaj A, Mishra SK, Kondaiah P et al (2008) Effect of the headgroup variation on the gene transfer properties of cholesterol based cationic lipids possessing ether linkage. Biochim Biophys Acta-Biomembranes 1778:1222–1236

    Article  CAS  Google Scholar 

  39. Soltan MK, Ghonaim HM, El Sadek M et al (2009) Design and synthesis of N-4, N-9-disubstituted spermines for non-viral siRNA delivery – structure–activity relationship studies of transfection efficiency versus toxicity. Pharm Res 26:286–295

    Article  PubMed  CAS  Google Scholar 

  40. Ghosh YK, Visweswariah SS, Bhattacharya S (2000) Nature of linkage between the cationic headgroup and cholesteryl skeleton controls gene transfection efficiency. FEBS Lett 473:341–344

    Article  PubMed  CAS  Google Scholar 

  41. Rajesh M, Sen J, Srujan M et al (2007) Dramatic influence of the orientation of linker between hydrophilic and hydrophobic lipid moiety in liposomal gene delivery. J Am Chem Soc 129:11408–11420

    Article  PubMed  CAS  Google Scholar 

  42. Ghosh YK, Visweswariah SS, Bhattacharya S (2002) Advantage of the ether linkage between the positive charge and the cholesteryl skeleton in cholesterol-based amphiphiles as vectors for gene delivery. Bioconjug Chem 13:378–384

    Article  PubMed  CAS  Google Scholar 

  43. Obata Y, Saito S, Takeda N et al (2009) Plasmid DNA-encapsulating liposomes: effect of a spacer between the cationic head group and hydrophobic moieties of the lipids on gene expression efficiency. Biochim Biophys Acta-Biomembranes 1788:1148–1158

    Article  CAS  Google Scholar 

  44. Horobin RW, Weissig V (2005) A QSAR-modeling perspective on cationic transfection lipids. 1. Predicting efficiency and understanding mechanisms. J Gene Med 7:1023–1034

    Article  PubMed  CAS  Google Scholar 

  45. Liu D, Qiao D, Li Z et al (2008) Structure–function relationship research of glycerol backbone-based cationic lipids for gene delivery. Chem Biol Drug Des 71:336–344

    Article  PubMed  CAS  Google Scholar 

  46. Koynova R, Tenchov B (2009) Cationic phospholipids – structure/transfection activity relationships. Soft Matter 5:3187–3200

    Article  CAS  Google Scholar 

  47. Tenchov BG, Wang L, Koynova R et al (2008) Modulation of a membrane lipid lamellar–nonlamellar phase transition by cationic lipids: a measure for transfection efficiency. Biochim Biophys Acta-Biomembranes 1778:2405–2412

    Article  CAS  Google Scholar 

  48. Das A, Niven R (2001) Use of perfluorocarbon (Fluorinert) to enhance reporter gene expression following intratracheal instillation into the lungs of Balb/c mice: implications for nebulized delivery of plasmids. J Pharm Sci 90:1336–1344

    Article  PubMed  CAS  Google Scholar 

  49. Faneca H, Cabrita AS, Simoes S et al (2007) Evaluation of the antitumoral effect mediated by IL-12 and HSV-tk genes when delivered by a novel lipid-based system. Biochim Biophys Acta-Biomembranes 1768:1093–1102

    Article  CAS  Google Scholar 

  50. Faneca H, Faustino A, de Lima MCP (2008) Synergistic antitumoral effect of vinblastine and HSV-Tk/GCV gene therapy mediated by albumin-associated cationic liposomes. J Control Release 126:175–184

    Article  PubMed  CAS  Google Scholar 

  51. Faneca H, Simoes S, de Lima MCP (2004) Association of albumin or protamine to lipoplexes: enhancement of transfection and resistance to serum. J Gene Med 6:681–692

    Article  PubMed  CAS  Google Scholar 

  52. Gorman CM, Aikawa M, Fox B et al (1997) Efficient in vivo delivery of DNA to pulmonary cells using the novel lipid EDMPC. Gene Ther 4:983–992

    Article  PubMed  CAS  Google Scholar 

  53. McDonald RJ, Liggitt HD, Roche L et al (1998) Aerosol delivery of lipid: DNA complexes to lungs of rhesus monkeys. Pharm Res 15:671–679

    Article  PubMed  CAS  Google Scholar 

  54. Noone PG, Hohneker KW, Zhou ZQ et al (2000) Safety and biological efficacy of a lipid–CFTR complex for gene transfer in the nasal epithelium of adult patients with cystic fibrosis. Mol Ther 1:105–114

    Article  PubMed  CAS  Google Scholar 

  55. Hyvonen Z, Plotniece A, Riene I et al (2000) Novel cationic amphiphilic 1,4-dihydropyridine derivatives for DNA delivery. Biochim Biophys Acta-Biomembranes 1509:451–466

    Article  CAS  Google Scholar 

  56. Yingyongnarongkul BE, Radchatawedchakoon W, Krajarng A et al (2009) High transfection efficiency and low toxicity cationic lipids with aminoglycerol-diamine conjugate. Bioorg Med Chem 17:176–188

    Article  PubMed  CAS  Google Scholar 

  57. Zhu L, Lu Y, Miller DD et al (2008) Structural and formulation factors influencing pyridinium lipid-based gene transfer. Bioconjug Chem 19:2499–2512

    Article  PubMed  CAS  Google Scholar 

  58. VanDerWoude I, Wagenaar A, Meekel AAP et al (1997) Novel pyridinium surfactants for efficient, nontoxic in vitro gene delivery. Proc Natl Acad Sci USA 94:1160–1165

    Article  CAS  Google Scholar 

  59. Heyes J, Palmer L, Bremner K et al (2005) Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids. J Control Release 107:276–287

    Article  PubMed  CAS  Google Scholar 

  60. Aberle AM, Bennett MJ, Malone RW et al (1996) The counterion influence on cationic lipid-mediated transfection of plasmid DNA. Biochim Biophys Acta-Lipids Lipid Metabolism 1299:281–283

    Article  Google Scholar 

  61. Koynova R, Brankov J, Tenchov B (1997) Modulation of lipid phase behavior by kosmotropic and chaotropic solutes – experiment and thermodynamic theory. Eur Biophys J Biophys Lett 25:261–274

    Article  CAS  Google Scholar 

  62. Boukhnikachvili T, AguerreChariol O, Airiau M et al (1997) Structure of in-serum transfecting DNA-cationic lipid complexes. FEBS Lett 409:188–194

    Article  PubMed  CAS  Google Scholar 

  63. Lasic DD, Strey H, Stuart MCA et al (1997) The structure of DNA–liposome complexes. J Am Chem Soc 119:832–833

    Article  CAS  Google Scholar 

  64. Radler JO, Koltover I, Salditt T et al (1997) Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science 275:810–814

    Article  PubMed  CAS  Google Scholar 

  65. Bruinsma R (1998) Electrostatics of DNA cationic lipid complexes: isoelectric instability. Eur Phys J B 4:75–88

    Google Scholar 

  66. Hirsch-Lerner D, Barenholz Y (1999) Hydration of lipoplexes commonly used in gene delivery: follow-up by laurdan fluorescence changes and quantification by differential scanning calorimetry. Biochim Biophys Acta-Biomembranes 1461:47–57

    Article  CAS  Google Scholar 

  67. Kennedy MT, Pozharski EV, Rakhmanova VA et al (2000) Factors governing the assembly of cationic phospholipid–DNA complexes. Biophys J 78:1620–1633

    Article  PubMed  CAS  Google Scholar 

  68. Pozharski EV, MacDonald RC (2007) Single lipoplex study of cationic lipoid-DNA, self-assembled complexes. Mol Pharm 4:962–974

    Article  PubMed  CAS  Google Scholar 

  69. Koynova R, MacDonald RC (2007) Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently. Biochim Biophys Acta-Biomembranes 1768:2373–2382

    Article  CAS  Google Scholar 

  70. Zelphati O, Nguyen C, Ferrari M et al (1998) Stable and monodisperse lipoplex formulations for gene delivery. Gene Ther 5:1272–1282

    Article  PubMed  CAS  Google Scholar 

  71. Takeuchi K, Ishihara M, Kawaura C et al (1996) Effect of zeta potential of cationic liposomes containing cationic cholesterol derivatives on gene transfection. FEBS Lett 397:207–209

    Article  PubMed  CAS  Google Scholar 

  72. Almofti MR, Harashima H, Shinohara Y et al (2003) Lipoplex size determines lipofection efficiency with or without serum. Mol Membr Biol 20:35–43

    Article  PubMed  CAS  Google Scholar 

  73. Ross PC, Hui SW (1999) Lipoplex size is a major determinant of in vitro lipofection efficiency. Gene Ther 6:651–659

    Article  PubMed  CAS  Google Scholar 

  74. Zhang JS, Huang L (2003) Cationic liposome–protamine–DNA complexes for gene delivery. Methods Enzymol 373:332–342

    Article  PubMed  CAS  Google Scholar 

  75. Rejman J, Oberle V, Zuhorn IS et al (2004) Size-dependent internalization of particles via the pathways of clathrin-and caveolae-mediated endocytosis. Biochem J 377:159–169

    Article  PubMed  CAS  Google Scholar 

  76. Hoekstra D, Rejman J, Wasungu L et al (2007) Gene delivery by cationic lipids: in and out of an endosome. Biochem Soc Trans 35:68–71

    Article  PubMed  CAS  Google Scholar 

  77. Lechardeur D, Verkman AS, Lukacs GL (2005) Intracellular routing of plasmid DNA during non-viral gene transfer. Adv Drug Deliv Rev 57:755–767

    Article  PubMed  CAS  Google Scholar 

  78. Prasad TK, Rangaraj N, Rao NM (2005) Quantitative aspects of endocytic activity in lipid-mediated transfections. FEBS Lett 579:2635–2642

    Article  PubMed  CAS  Google Scholar 

  79. Elouahabi A, Ruysschaert JM (2005) Formation and intracellular trafficking of lipoplexes and polyplexes. Mol Ther 11:336–347

    Article  PubMed  CAS  Google Scholar 

  80. Tyagi P, Wu PC, Chancellor M et al (2006) Recent advances in intravesical drug/gene delivery. Mol Pharm 3:369–379

    Article  PubMed  CAS  Google Scholar 

  81. Koynova R, Tarahovsky Y, Wang L et al (2007) Lipoplex formulation of superior efficacy exhibits high surface activity and fusogenicity, and readily releases DNA. Biochim Biophys Acta-Biomembranes 1768:375–386

    Article  CAS  Google Scholar 

  82. Salditt T, Koltover I, Radler JO et al (1997) Two-dimensional smectic ordering of linear DNA chains in self-assembled DNA–cationic liposome mixtures. Phys Rev Lett 79:2582–2585

    Article  CAS  Google Scholar 

  83. Artzner F, Zantl R, Rapp G et al (1998) Observation of a rectangular columnar phase in condensed lamellar cationic lipid–DNA complexes. Phys Rev Lett 81:5015–5018

    Article  CAS  Google Scholar 

  84. Koynova R, MacDonald RC (2004) Columnar DNA superlattices in lamellar o-ethylphosphatidylcholine lipoplexes: mechanism of the gel-liquid crystalline lipid phase transition. Nano Lett 4:1475–1479

    Article  CAS  Google Scholar 

  85. Congiu A, Pozzi D, Esposito C et al (2004) Correlation between structure and transfection efficiency: a study of DC-Chol-DOPE/DNA complexes. Coll Surf B Biointerfaces 36:43–48

    Article  CAS  Google Scholar 

  86. Koltover I, Salditt T, Radler JO et al (1998) An inverted hexagonal phase of cationic liposome–DNA complexes related to DNA release and delivery. Science 281:78–81

    Article  PubMed  CAS  Google Scholar 

  87. Smisterova J, Wagenaar A, Stuart MCA et al (2001) Molecular shape of the cationic lipid controls the structure of cationic lipid/dioleylphosphatidylethanolamine-DNA complexes and the efficiency of gene delivery. J Biol Chem 276:47615–47622

    Article  PubMed  CAS  Google Scholar 

  88. Francescangeli O, Pisani M, Stanic V et al (2004) Evidence of an inverted hexagonal phase in self-assembled phospholipid-DNA-metal complexes. Europhys Lett 67:669–675

    Article  CAS  Google Scholar 

  89. Caracciolo G, Caminiti R (2005) Do DC-Chol/DOPE-DNA complexes really form an inverted hexagonal phase? Chem Phys Lett 411:327–332

    Article  CAS  Google Scholar 

  90. Caracciolo G, Pozzi D, Caminiti R et al (2003) Structural characterization of a new lipid/DNA complex showing a selective transfection efficiency in ovarian cancer cells. Eur Phys J E 10:331–336

    Article  PubMed  CAS  Google Scholar 

  91. Lin AJ, Slack NL, Ahmad A et al (2003) Three-dimensional imaging of lipid gene-carriers: membrane charge density controls universal transfection behavior in lamellar cationic liposome–DNA complexes. Biophys J 84:3307–3316

    Article  PubMed  CAS  Google Scholar 

  92. Ross PC, Hensen ML, Supabphol R et al (1998) Multilamellar cationic liposomes are efficient vectors for in vitro gene transfer in serum. J Liposome Res 8:499–520

    Article  CAS  Google Scholar 

  93. Simberg D, Danino D, Talmon Y et al (2003) Phase behavior, DNA ordering and size instability of cationic lipoplexes: relevance to optimal transfection activity. J Liposome Res 13:86–87

    Google Scholar 

  94. Legendre JY, Szoka FC (1992) Delivery of plasmid DNA into mammalian-cell lines using Ph-sensitive liposomes – comparison with cationic liposomes. Pharm Res 9:1235–1242

    Article  PubMed  CAS  Google Scholar 

  95. Zabner J, Fasbender AJ, Moninger T et al (1995) Cellular and molecular barriers to gene-transfer by a cationic lipid. J Biol Chem 270:18997–19007

    Article  PubMed  CAS  Google Scholar 

  96. Zhou XH, Huang L (1994) DNA transfection mediated by cationic liposomes containing lipopolylysine – characterization and mechanism of action. Biochim Biophys Acta-Biomembranes 1189:195–203

    Article  CAS  Google Scholar 

  97. Ashley GW, Shida MM, Qiu R et al (1996) Phosphatidylcholinium compounds: a new class of cationic phospholipids with transfection activin and unusual physical properties (abstract). Biophys J 70:88-A

    Google Scholar 

  98. Tarahovsky YS, Koynova R, MacDonald RC (2004) DNA release from lipoplexes by anionic lipids: correlation with lipid mesomorphism, interfacial curvature, and membrane fusion. Biophys J 87:1054–1064

    Article  PubMed  CAS  Google Scholar 

  99. Xu YH, Szoka FC (1996) Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 35:5616–5623

    Article  PubMed  CAS  Google Scholar 

  100. Zelphati O, Szoka FC (1996) Mechanism of oligonucleotide release from cationic liposomes. Proc Natl Acad Sci USA 93:11493–11498

    Article  PubMed  CAS  Google Scholar 

  101. Koynova R, Tenchov B (2009) Phase transitions of lipids. In: Begley TP (ed) Wiley encyclopedia of chemical biology. Wiley, Hoboken, NJ, pp 601–615

    Google Scholar 

  102. Seddon JM, Templer RH (1995) Polymorphism of lipid–water systems. In: Lipowsky R, Sackmann E (eds) Handbook of biological physics. Elsevier Science, Amsterdam, pp 97–160

    Google Scholar 

  103. Hafez IM, Maurer N, Cullis PR (2001) On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids. Gene Ther 8:1188–1196

    Article  PubMed  CAS  Google Scholar 

  104. Koynova R, MacDonald RC (2003) Mixtures of cationic lipid O-ethylphosphatidylcholine with membrane lipids and DNA: phase diagrams. Biophys J 85:2449–2465

    Article  PubMed  CAS  Google Scholar 

  105. Lewis RNAH, McElhaney RN (2000) Surface charge markedly attenuates the nonlamellar phase-forming propensities of lipid bilayer membranes: calorimetric and P-31-nuclear magnetic resonance studies of mixtures of cationic, anionic, and zwitterionic lipids. Biophys J 79:1455–1464

    Article  PubMed  CAS  Google Scholar 

  106. Tarahovsky YS, Arsenault AL, MacDonald RC et al (2000) Electrostatic control of phospholipid polymorphism. Biophys J 79:3193–3200

    Article  PubMed  CAS  Google Scholar 

  107. Kleinschmidt JH, Tamm LK (2002) Structural transitions in short-chain lipid assemblies studied by P-31-NMR spectroscopy. Biophys J 83:994–1003

    Article  PubMed  CAS  Google Scholar 

  108. Koynova R, MacDonald RC (2005) Lipid transfer between cationic vesicles and lipid-DNA lipoplexes. Effect of serum. Biochim Biophys Acta-Biomembranes 1714:63–70

    Article  CAS  Google Scholar 

  109. Simoes S, Pires P, Duzgunes N et al (1999) Cationic liposomes as gene transfer vectors: barriers to successful application in gene therapy. Curr Opin Mol Ther 1:147–157

    PubMed  CAS  Google Scholar 

  110. Sen GL, Blau HM (2005) Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat Cell Biol 7:633–636

    Article  PubMed  CAS  Google Scholar 

  111. Lu JJ, Langer R, Chen JZ (2009) A novel mechanism is involved in cationic lipid-mediated functional siRNA delivery. Mol Pharm 6:763–771

    Article  PubMed  CAS  Google Scholar 

  112. Koynova R, Wang L, MacDonald RC (2006) An intracellular lamellar – nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents. Proc Natl Acad Sci USA 103:14373–14378

    Article  PubMed  CAS  Google Scholar 

  113. Lipid Data Bank (2000) http://www.lipidat.ul.ie/

  114. Anderson DM, Gruner SM, Leibler S (1988) Geometrical aspects of the frustration in the cubic phases of lyotropic liquid-crystals. Proc Natl Acad Sci USA 85:5364–5368

    Article  PubMed  CAS  Google Scholar 

  115. Shearman GC, Ces O, Templer RH et al (2006) Inverse lyotropic phases of lipids and membrane curvature. J Phys Condens Matter 18:S1105–S1124

    Article  PubMed  CAS  Google Scholar 

  116. Templer RH, Seddon JM, Duesing PM et al (1998) Modeling the phase behavior of the inverse hexagonal and inverse bicontinuous cubic phases in 2:1 fatty acid phosphatidylcholine mixtures. J Phys Chem B 102:7262–7271

    Article  CAS  Google Scholar 

  117. Siegel DP (2005) Bicontinuous Liquid Crystals. In: Lynch ML, Spicer PT (eds) Bicontinuous liquid crystals. Taylor & Francis Group, CRC Press, Boca Raton, pp 59–98, Chap 4

    Chapter  Google Scholar 

  118. Siegel DP, Epand RM (1997) The mechanism of lamellar-to-inverted hexagonal phase transitions in phosphatidylethanolamine: implications for membrane fusion mechanisms. Biophys J 73:3089–3111

    Article  PubMed  CAS  Google Scholar 

  119. Yang L, Huang HW (2002) Observation of a membrane fusion intermediate structure. Science 297:1877–1879

    Article  PubMed  CAS  Google Scholar 

  120. Farhood H, Serbina N, Huang L (1995) The role of dioleoyl phosphatidylethanolamine in cationic liposome-mediated gene-transfer. Biochim Biophys Acta-Biomembranes 1235:289–295

    Article  Google Scholar 

  121. Zuhorn IS, Oberle V, Visser WH et al (2002) Phase behavior of cationic amphiphiles and their mixtures with helper lipid influences lipoplex shape, DNA translocation, and transfection efficiency. Biophys J 83:2096–2108

    Article  PubMed  CAS  Google Scholar 

  122. Fletcher S, Ahmad A, Price WS et al (2008) Biophysical properties of CDAN/DOPE-analogue lipoplexes account for enhanced gene delivery. Chembiochem 9:455–463

    Article  PubMed  CAS  Google Scholar 

  123. Hong KL, Zheng WW, Baker A et al (1997) Stabilization of cationic liposome–plasmid DNA complexes by polyamines and poly(ethylene glycol)-phospholipid conjugates for efficient in vivo gene delivery. FEBS Lett 400:233–237

    Article  PubMed  CAS  Google Scholar 

  124. Liu Y, Mounkes LC, Liggitt HD et al (1997) Factors influencing the efficiency of cationic liposome-mediated intravenous gene delivery. Nat Biotechnol 15:167–173

    Article  PubMed  CAS  Google Scholar 

  125. Smith JG, Wedeking T, Vernachio JH et al (1998) Characterization and in vivo testing of a heterogeneous cationic lipid–DNA formulation. Pharm Res 15:1356–1363

    Article  PubMed  CAS  Google Scholar 

  126. Sternberg B, Hong KL, Zheng WW et al (1998) Ultrastructural characterization of cationic liposome–DNA complexes showing enhanced stability in serum and high transfection activity in vivo. Biochim Biophys Acta-Biomembranes 1375:23–35

    Article  CAS  Google Scholar 

  127. Wang JK, Guo X, Xu YH et al (1998) Synthesis and characterization of long chain alkyl acyl carnitine esters. Potentially biodegradable cationic lipids for use in gene delivery. J Med Chem 41:2207–2215

    Article  PubMed  CAS  Google Scholar 

  128. Regelin AE, Fankhaenel S, Gurtesch L et al (2000) Biophysical and lipofection studies of DOTAP analogs. Biochim Biophys Acta-Biomembranes 1464:151–164

    Article  CAS  Google Scholar 

  129. Jiao J (2008) Polyoxyethylated nonionic surfactants and their applications in topical ocular drug delivery. Adv Drug Deliv Rev 60:1663–1673

    Article  PubMed  CAS  Google Scholar 

  130. Wang L, MacDonald RC (2004) New strategy for transfection: mixtures of medium-chain and long-chain cationic lipids synergistically enhance transfection. Gene Ther 11:1358–1362

    Article  PubMed  CAS  Google Scholar 

  131. Koynova R, Wang L, Tarahovsky Y et al (2005) Lipid phase control of DNA delivery. Bioconjug Chem 16:1335–1339

    Article  PubMed  CAS  Google Scholar 

  132. Koynova R, Wang L, MacDonald RC (2007) Synergy in lipofection by cationic lipid mixtures: superior activity at the gel–liquid crystalline phase transition. J Phys Chem B 111:7786–7795

    Article  PubMed  CAS  Google Scholar 

  133. Wagner E, Culmsee C, Boeckle S (2005) Targeting of polyplexes: toward synthetic virus vector systems. Adv Genet 53:333–354

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The present work was supported by NSF grant EEC-0425626 and in part by NIH grant CA119341.

Author information

Authors and Affiliations

  1. Ohio State University College of Pharmacy, 517 Parks Hall, 500 W 12th Ave, Columbus, OH, 43210, USA

    Rumiana Koynova & Boris Tenchov

  2. Northwestern University, Evanston, IL, USA

    Rumiana Koynova

  3. Bulgarian Academy of Sciences, Sofia, Bulgaria

    Boris Tenchov

Authors
  1. Rumiana Koynova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Boris Tenchov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rumiana Koynova .

Editor information

Editors and Affiliations

  1. Cell Biology/RNAi, QIAGEN GmbH, Qiagen Str. 1, Hilden, 40724, Germany

    Wolfgang Bielke

  2. Cell Biology/RNAi, QIAGEN GmbH, Qiagen Str. 1, Hilden, 40724, Germany

    Christoph Erbacher

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Koynova, R., Tenchov, B. (2010). Cationic Lipids: Molecular Structure/Transfection Activity Relationships and Interactions with Biomembranes. In: Bielke, W., Erbacher, C. (eds) Nucleic Acid Transfection. Topics in Current Chemistry, vol 296. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2010_67

Download citation

Publish with us

Policies and ethics

Search

Navigation