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Cationic liposome/DNA complexes: from structure to interactions with cellular membranes

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Abstract

Gene-based therapeutic approaches are based upon the concept that, if a disease is caused by a mutation in a gene, then adding back the wild-type gene should restore regular function and attenuate the disease phenotype. To deliver the gene of interest, both viral and nonviral vectors are used. Viruses are efficient, but their application is impeded by detrimental side-effects. Among nonviral vectors, cationic liposomes are the most promising candidates for gene delivery. They form stable complexes with polyanionic DNA (lipoplexes). Despite several advantages over viral vectors, the transfection efficiency (TE) of lipoplexes is too low compared with those of engineered viral vectors. This is due to lack of knowledge about the interactions between complexes and cellular components. Rational design of efficient lipoplexes therefore requires deeper comprehension of the interactions between the vector and the DNA as well as the cellular pathways and mechanisms involved. The importance of the lipoplex structure in biological function is revealed in the application of synchrotron small-angle X-ray scattering in combination with functional TE measurements. According to current understanding, the structure of lipoplexes can change upon interaction with cellular membranes and such changes affect the delivery efficiency. Recently, a correlation between the mechanism of gene release from complexes, the structure, and the physical and chemical parameters of the complexes has been established. Studies aimed at correlating structure and activity of lipoplexes are reviewed herein. This is a fundamental step towards rational design of highly efficient lipid gene vectors.

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References

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

    CAS  Google Scholar 

  • Balazs DA, Godbey WT (2011) Liposomes for use in gene delivery. J Drug Deliv. doi:10.1155/2011/326497

  • Barreleiro PCA, Lindman B (2003) The kinetics of DNA-cationic vesicle complex formation. J Phys Chem B 107:6208–6213

    CAS  Google Scholar 

  • Barreleiro PCA, May RP, Lindman B (2002) Mechanism of formation of DNA-cationic vesicle complexes. Faraday Discuss 122:191–201

    Google Scholar 

  • Behr JP (1994) Gene transfer with synthetic cationic amphiphiles: prospects for gene therapy. Bioconjugate Chem 5:382–389

    Google Scholar 

  • Boktov J, Hirsch-Lerner D, Barenholz Y et al (2007) Characterization of the interplay between the main factors contributing to lipoplex-mediated transfection in cell cultures. J Gene Med 9:884–893

    PubMed  CAS  Google Scholar 

  • Both G, Alexander I, Fletcher S, Nicolson TJ, Rasko JE, Wilton SD, Symonds G (2011) Gene therapy: therapeutic applications and relevance to pathology. Pathology 43:642–656

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Caracciolo G, Caminiti R (2004) DNA–DNA electrostatic interactions within cationic lipid/DNA lamellar complexes. Chem Phys Lett 400:314–319

    CAS  Google Scholar 

  • Caracciolo G, Caminiti R, Pozzi D, Friello M, Boffi F, Congiu Castellano A (2002) Self-assembly of cationic liposomes–DNA complexes: a structural and thermodynamic study by EDXD. Chem Phys Lett 351:222–228

    CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R, Congiu Castellano A (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

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Amenitsch H, Caminiti R (2005a) Multicomponent cationic lipid-DNA complex formation: role of lipid mixing. Langmuir 21:11582–11587

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R, Amenitsch H (2005b) Lipid mixing upon deoxyribonucleic acid-induced liposomes fusion investigated by synchrotron small-angle X-ray scattering. Appl Phys Lett 87:133901

    Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R, Amenitsch H (2006a) Two-dimensional lipid mixing entropy regulates the formation of multicomponent lipoplexes. J Phys Chem B 110:20829–20835

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R, Amenitsch H (2006b) Formation of overcharged cationic lipid/DNA complexes. Chem Phys Lett 429:250–254

    CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R (2006c) Is the formation of cationic lipid-DNA complexes a thermodynamically driven phenomenon? Structure and phase behavior of DC-Chol/DNA complexes say not. Appl Phys Lett 89:43901

    Google Scholar 

  • Caracciolo G, Marchini C, Pozzi D, Caminiti R, Amenitsch H, Montani M, Amici A (2007a) Structural stability against disintegration by anionic lipids rationalizes the efficiency of cationic liposome/DNA complexes. Langmuir 23:4498–4508

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R, Marchini C, Montani M, Amici A, Amenitsch H (2007b) Transfection efficiency boost by designer multicomponent lipoplexes. Biochim Biophys Acta 1768:2280–2292

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Amenitsch H, Caminiti R (2007c) Interaction of lipoplexes with anionic lipids resulting in DNA release is a two-stage process. Langmuir 23:8713–8717

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R, Mancini G, Luciani P, Amenitsch H (2007d) Rectangular DNA superlattices in the liquid crystalline phase of cationic Gemini/phospholipid-DNA complexes. J Am Chem Soc 129:10092–10093

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R, Marchini C, Montani M, Amici A, Amenitsch H (2008a) Enhanced transfection efficiency of multicomponent lipoplexes in the regime of optimal membrane charge density. J Phys Chem B 112:11298–11304

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Caminiti R, Marchini C, Montani M, Amenitsch H (2008b) Effect of pH on the structure of lipoplexes. J Appl Phys 104:014701:1–014701:7

    Google Scholar 

  • Caracciolo G, Caminiti R, Digman MA, Gratton E, Sanchez S (2009) Efficient escape from endosomes determines the superior efficiency of multicomponent lipoplexes. J Phys Chem B 113:4995–4997

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Pozzi D, Amici A, Amenitsch H (2010a) Universality of DNA adsorption behavior on the cationic membranes of nanolipoplexes. J Phys Chem B 114:2028–2032

    PubMed  CAS  Google Scholar 

  • Caracciolo G, Callipo L, Candeloro De Sanctis S, Cavaliere C, Pozzi D, Laganà L (2010b) Surface adsorption of protein corona controls the cell internalization mechanism of DC-Chol–DOPE/DNA lipoplexes in serum. Biochim Biophys Acta 1798:536–543

    PubMed  CAS  Google Scholar 

  • Cardarelli F, Pozzi D, Bifone A, Marchini C, Caracciolo G (2012) Cholesterol-dependent macropinocytosis and endosomal escape control the transfection efficiency of lipoplexes in CHO living cells. Mol Pharm 9:334–340

    PubMed  CAS  Google Scholar 

  • Cherstvy AG (2007) Electrostatics of DNA complexes with cationic lipid membranes. J Phys Chem B 111:7914–7927

    PubMed  CAS  Google Scholar 

  • Denèfle PP (2011) Introduction to gene therapy: a clinical aftermath. Methods Mol Biol 737:27–44

    PubMed  Google Scholar 

  • Ewert KK, Ahmad A, Evans HM, Safinya CR (2005) Cationic lipid–DNA complexes for non-viral gene therapy: relating supramolecular structures to cellular pathways. Expert Opin Biol Ther 5:33–53

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  • Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84:7413–7417

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Gao L, Cao J, Fang W (2010) Self-assembly of lamellar lipid-DNA complexes simulated by explicit solvent counterion model. J Phys Chem B 114:7261–7264

    PubMed  CAS  Google Scholar 

  • Glover DJ (2011) Artificial viruses: exploiting viral trafficking for therapeutics. Infect Disord Drug Targets 12:68–80. PMID: 22034936

    Google Scholar 

  • Gonçalves C, Mennesson E, Fuchs R et al (2004a) Macropinocytosis of polyplexes and recycling of plasmid via the clathrin-dependent pathway impair the transfection efficiency of human hepatocarcinoma cells. Mol Ther 10:373–385

    PubMed  Google Scholar 

  • Gonçalves E, Debs RJ, Heath TD (2004b) The effect of liposome size on the final lipid/DNA ratio of cationic lipoplexes. Biophys J 86:1554–1563

    PubMed  Google Scholar 

  • Gregoriadis G (2001) Liposome technology. Francis/Informa, New York

    Google Scholar 

  • Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, Radford I, Villeval JL, Fraser CC, Cavazzana-Calvo M et al (2003) A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 348:255–256

    PubMed  Google Scholar 

  • Hafez IM, Ansell S, Cullis PR (2000) Tunable pH-sensitive liposomes composed of mixtures of cationic and anionic lipids. Biophys J 79:1438–1446

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Harries D, May S, Gelbart WM, Ben-Shaul A (1998) Structure, stability, and thermodynamics of lamellar DNA-lipid complexes. Biophys J 75:159–173

    PubMed  CAS  Google Scholar 

  • Hart SL (2010) Multifunctional nanocomplexes for gene transfer and gene therapy. Cell Biol Toxicol 26:69–81

    PubMed  CAS  Google Scholar 

  • Hayes ME, Gorelov AV, Dawson KA (2001) DNA-induced fusion of phosphatidylcholine vesicles. Prog Colloid Polym Sci 118:243–247

    CAS  Google Scholar 

  • Henriques AM, Madeira C, Fevereiro M, Prazeresa DMF, Aires-Barrosa MR, Monteiro GA (2009) Effect of cationic liposomes/DNA charge ratio on gene expression and antibody response of a candidate DNA vaccine against Maedi Visna virus. Int J Pharm 377:92–98

    PubMed  CAS  Google Scholar 

  • Herringson TP, Patlolla RR, Altin JG (2009) Targeting of plasmid DNA-lipoplexes to cells with molecules anchored via a metal chelator lipid. J Gene Med 11:1048–1063

    PubMed  CAS  Google Scholar 

  • Hirsch-Lerner D, Zhang M, Eliyahu H, Ferrari ME, Wheeler CJ, Barenholz Y (2005) Effect of “helper lipid” on lipoplex electrostatics. Biochim Biophys Acta 1714:71–84

    PubMed  CAS  Google Scholar 

  • Hoekstra D, Rejman J, Wasungu L, Shi F, Zuhorn IS (2007) Gene delivery by cationic lipids: in and out of an endosome. Biochem Soc Trans 35:68–71

    PubMed  CAS  Google Scholar 

  • Huebner S, Battersby BJ, Grimm R, Cevc G (1999) Lipid-DNA complex formation: reorganization and rupture of lipid vesicles in the presence of DNA as observed by cryoelectron microscopy. Biophys J 76:3158–3166

    PubMed  CAS  Google Scholar 

  • Hui SW, Langner M, Zhao YL, Ross P, Hurley E, Chan K (1996) The role of helper lipids in cationic liposome-mediated gene transfer. Biophys J 71:590–599

    PubMed  CAS  Google Scholar 

  • Israelachvili JN, Mitchell DJ, Ninham BW (1977) Theory of self-assembly of lipid bilayers and vesicles. Biochim Biophys Acta 470:185–201

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kasson PM, Pande VS (2007) Control of membrane fusion mechanism by lipid composition: predictions from ensemble molecular dynamics. PLoS Comput Biol 3:2228–2238

    CAS  Google Scholar 

  • Kay MA (2011) State-of-the-art gene-based therapies: the road ahead. Nat Rev Genet 12:316–328

    PubMed  CAS  Google Scholar 

  • Kennedy MT, Pozhaski EV, Rakhmanova VA, MacDonald RC (2000) Factors governing the assembly of cationic phospholipid-DNA complexes. Biophys J 78:1620–1633

    PubMed  CAS  Google Scholar 

  • Khalil IA, Kogure K, Akita H, Harashima H (2006) Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery. Pharmacol Rev 58:32–45

    PubMed  CAS  Google Scholar 

  • Kirkham M, Parton RG (2005) Clathrin-independent endocytosis: new insights into caveolae and non-caveolar lipid raft carriers. Biochim Biophys Acta 1746:350–363

    CAS  Google Scholar 

  • Koltover I, Salditt T, Rädler JO, Safinya CR (1998) An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science 281:78–81

    PubMed  CAS  Google Scholar 

  • Koltover I, Salditt T, Safinya CR (1999) Phase diagram, stability, and overcharging of lamellar cationic lipid-DNA self-assembled complexes. Biophys J 77:915–924

    PubMed  CAS  Google Scholar 

  • Koltover I, Wagner K, Safinya CR (2000) DNA condensation in two dimensions. Proc Natl Acad Sci 97:14046–14051

    PubMed  CAS  Google Scholar 

  • Kooijman EE, Carter KM, van Laar EG, Chupin V, Burger KNJ, de Kruijf B (2005) What makes the bioactive lipids phosphatidic acid and lysophosphatidic acid so special? Biochemistry 44:17007–17015

    PubMed  CAS  Google Scholar 

  • Koynova R (2008) Lipid phase eye view of lipofection. Cationic phosphatidylcholine derivatives as efficient DNA carriers for gene delivery. Lipid Insights 2:41–59

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Koynova R, MacDonald RC (2004) Columnar DNA superlattices in lamellar /O/-ethylphosphatidylcholine lipoplexes. Nano Lett 4:1475–1479

    Google Scholar 

  • 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 1768:2373–2382

    PubMed  CAS  Google Scholar 

  • Koynova R, Wang L, Tarahovsky Y, MacDonald RC (2005) Lipid phase control of DNA delivery. Bioconjugate Chem 16:1335–1339

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kreiss P, Cameron B, Rangara R, Mailhe P, Aguerre-Charriol O, Airiau M, Scherman D, Crouzet J, Pitard B (1999) Plasmid DNA size does not affect the physicochemical properties of lipoplexes but modulates gene transfer efficiency. Nucleic Acids Res 27:3792–3798

    PubMed  CAS  Google Scholar 

  • Krishnaswamy R, Pabst G, Rappolt M, Raghunathan VA, Sood AK (2006) Structure of DNA-CTAB-hexanol complexes. Phys Rev E 73:031904

    Google Scholar 

  • Labas R, Beilvert F, Barteau B, David S, Chèvre R, Pitard B (2009) Nature as a source of inspiration for cationic lipid synthesis. Genetica 138:153–168

    PubMed  Google Scholar 

  • Le Bihan O, Chèvre R, Mornet S, Garnier B, Pitard B, Lambert O (2011) Probing the in vitro mechanism of action of cationic lipid/DNA lipoplexes at a nanometric scale. Nucleic Acids Res 39:1595–1609

    PubMed  Google Scholar 

  • Le Bret M, Zimm BH (1984) Monte Carlo determination of the distribution of ions about a cylindrical polyelectrolyte. Biopolymers 23:271–285

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lin AJ, Slack NL, Ahmad A, Koltover I, George CX, Samuel CE, Safinya CR (2000) Structure and structure-function studies of lipid/plasmid DNA complexes. J Drug Target 8:13–27

    PubMed  CAS  Google Scholar 

  • Lynch I, Salvati A, Dawson KA (2009) Protein-nanoparticle interactions: what does the cell see? Nat Nanotechnol 4:546–547

    PubMed  CAS  Google Scholar 

  • Ma B, Zhang S, Jiang H, Zhao B, Lv H (2007) Lipoplex morphologies and their influences on transfection efficiency in gene delivery. J Control Release 123:184–194

    PubMed  CAS  Google Scholar 

  • Madeira C, Loura LM, Aires-Barros MR, Fedorov A, Prieto M (2003) Characterization of DNA/lipid complexes by fluorescence resonance energy transfer. Biophys J 85:3106–3119

    PubMed  CAS  Google Scholar 

  • Madeira C, Loura LM, Prieto M, Fedorov A, Aires-Barros MR (2007) Liposome complexation efficiency monitored by FRET: effect of charge ratio, helper lipid and plasmid size. Eur Biophys J 36:609–620

    PubMed  CAS  Google Scholar 

  • Maitani Y, Igarashi S, Sato M, Hattori Y (2007) Cationic liposome (DC-Chol/DOPE = 1:2) and a modified ethanol injection method to prepare liposomes, increased gene expression. Int J Pharm 342:33–39

    PubMed  CAS  Google Scholar 

  • Manning GS (1969) Limiting laws and counterion condensation in polyelectrolytesolutions. II. An analysisbasedontheMayerionic solution theory. J Chem Phys 51:3249–3252

    CAS  Google Scholar 

  • Manning GS (1978) The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Q Rev Biophys 11:179–246

    PubMed  CAS  Google Scholar 

  • Marchini C, Montani M, Amici A, Pozzi D, Caminiti R, Caracciolo G (2009a) Surface area of lipid membranes regulates the DNA-binding capacity of cationic liposomes. Appl Phys Lett 94:033903:1–033903:3

    Google Scholar 

  • Marchini C, Montani M, Amici A, Amenitsch H, Marianecci C, Pozzi D, Caracciolo G (2009b) Structural stability and increase in size rationalize the efficiency of lipoplexes in serum. Langmuir 25:3013–3021

    Google Scholar 

  • Marchini C, Pozzi D, Alfonsi C, Montani M, Amici A, Amenitsch H, Caracciolo G (2010) Coupling between lipoplex and plasma membrane lipid composition: a trojan horse for cell entry? Langmuir 26:13867–13873

    PubMed  CAS  Google Scholar 

  • Marchini C, Pozzi D, Montani M, Alfonsi C, Amici A, Candeloro De Sanctis S, Digman MA, Sanchez SS, Gratton E, Amenitsch H, Fabbretti A, Gualerzi CO, Caracciolo G (2011) Role of temperature-independent lipoplex-cell membrane interactions in the efficiency boost of multicomponent lipoplexes. Cancer Gene Ther 18:543–552

    PubMed  CAS  Google Scholar 

  • May S, Ben-Shaul A (1997) DNA-lipid complexes: stability of honeycomb-like and spaghetti-like structures. Biophys J 73:2427–2440

    PubMed  CAS  Google Scholar 

  • May S, Ben-Shaul A (2004) Modeling of cationic lipid-DNA complexes. Curr Med Chem 11:151–167

    PubMed  CAS  Google Scholar 

  • May S, Harries D, Ben-Shaul A (2000) The phase behavior of cationic lipid-DNA complexes. Biophys J 78:1681–1697

    PubMed  CAS  Google Scholar 

  • McManus JJ, Rädler JO, Dawson KA (2004) Observation of a rectangular columnar phase in a DNA–calcium–zwitterionic lipid complex. J Am Chem Soc 126:15966–15967

    PubMed  CAS  Google Scholar 

  • Melief CJ, O’Shea JJ, Stroncek DF (2011) Summit on cell therapy for cancer: the importance of the interaction of multiple disciplines to advance clinical therapy. J Transl Med 9:1–5

    Google Scholar 

  • Minchin RF, Yang S (2010) Endosomal disruptors in non-viral gene delivery. Expert Opin Drug Deliv 7:331–339

    PubMed  CAS  Google Scholar 

  • Mislick KA, Baldeschwieler JD (1996) Evidence for the role of proteoglycans in cation-mediated gene transfer. Proc Natl Acad Sci USA 93:12349–12354

    PubMed  CAS  Google Scholar 

  • Mok KW, Cullis PR (1997) Structural and fusogenic properties of cationic liposomes in the presence of plasmid DNA. Biophys J 73:2534–2545

    PubMed  CAS  Google Scholar 

  • Monopoli MP, Walczyk D, Campbell A, Elia G, Lynch I, Bombelli FB, Dawson KA (2011a) Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J Am Chem Soc 133:2525–2534

    PubMed  CAS  Google Scholar 

  • Monopoli MP, Bombelli FB, Dawson KA (2011b) Nanobiotechnology: nanoparticle coronas take shape. Nat Nanotechnol 6:11–12

    PubMed  CAS  Google Scholar 

  • Montier T, Benvegnu T, Jaffrès PA, Yaouanc JJ, Lehn P (2008) Progress in cationic lipid-mediated gene transfection: a series of bio-inspired lipids as an example. Curr Gene Ther 8:296–312

    PubMed  CAS  Google Scholar 

  • Mortazavi SM, Mohammadabadi MR, Khosravi-Darani K, Mozafari MR (2007) Preparation of liposomal gene therapy vectors by a scalable method without using volatile solvents or detergents. J Biotechnol 129:604–613

    PubMed  CAS  Google Scholar 

  • Muñoz-Úbeda M, Misra SK, Barrán-Berdón AL, Aicart-Ramos C, Sierra MB, Biswas J, Kondaiah P, Junquera E, Bhattacharya S, Aicart E (2011) Why is less cationic lipid required to prepare lipoplexes from plasmid DNA than linear DNA in gene therapy? J Am Chem Soc 133:18014–18017

    PubMed  Google Scholar 

  • Ondrej V, Lukasova E, Falk M, Kozubek S (2007) The role of actin and microtubule networks in plasmid DNA intracellular trafficking. Acta Biochim Pol 54:657–663

    PubMed  CAS  Google Scholar 

  • Pozharski EV, MacDonald RC (2005) Analysis of the structure and composition of individual lipoplex particles by flow fluorometry. Anal Biochem 341:230–240

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Pozzi D, Caracciolo G, Caminiti R, Candeloro De Sanctis S, Amenitsch H, Marchini C, Montani M, Amici A (2009) Toward the rational design of lipid gene vectors: shape coupling between lipoplex and anionic cellular lipids controls the phase evolution of lipoplexes and the efficiency of DNA release. Appl Mat Inter 1:2237–2249

    CAS  Google Scholar 

  • Rädler JO, Koltover I, Salditt T, Safinya CR (1997) Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science 275:810–814

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Resina S, Prevot P, Thierry AR (2009) Physico-chemical characteristics of lipoplexes influence cell uptake mechanisms and transfection efficacy. PLoS One 4:e6058:1–11

    Google Scholar 

  • Rodowicz KA, Francisco H, Layton B (2010) Determination of the mechanical properties of DOPC:DOPS liposomes using an image procession algorithm and micropipette-aspiration techniques. Chem Phys Lipids 163:787–793

    PubMed  Google Scholar 

  • Rodríguez-Pulido A, Martín-Molina A, Rodríguez-Beas C, Llorca O, Aicart E, Junquera E (2009) A theoretical and experimental approach to the compaction process of DNA by dioctadecyldimethylammonium bromide/zwitterionic mixed liposomes. J Phys Chem B 113:15648–15661

    PubMed  Google Scholar 

  • Ruthardt N, Lamb DC, Bräuchle C (2011) Single-particle tracking as a quantitative microscopy-based approach to unravel cell entry mechanisms of viruses and pharmaceutical nanoparticles. Mol Ther 19:1199–1211

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Samadikhah HR, Majidi A, Nikkhah M, Hosseinkhani S (2011) Preparation, characterization, and efficient transfection of cationic liposomes and nanomagnetic cationic liposomes. Int J Nanomed 6:2275–2283

    CAS  Google Scholar 

  • Simberg D, Weisman S, Talmon Y, Barenholz Y (2004) DOTAP (and other cationic lipids): chemistry, biophysics, and transfection. Crit Rev Ther Drug Carrier Syst 21:257–317

    PubMed  CAS  Google Scholar 

  • Simoes S, Slepushkin V, Pires P, Gaspar R, de Lima MP, Duzgunes N (1999) Mechanisms of gene transfer mediated by lipoplexes associated with targeting ligands or pH-sensitive peptides. Gene Ther 6:1798–1807

    PubMed  CAS  Google Scholar 

  • Smisterová J, Wagenaar A, Stuart MC, Polushkin E, ten Brinke G, Hulst R, Engberts JB, Hoekstra D (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

    PubMed  Google Scholar 

  • Tandia BM, Lonez C, Vandenbranden M, Ruysschaert JM, Elouahabi A (2005) Lipid mixing between lipoplexes and plasma lipoproteins is a major barrier for intravenous transfection mediated by cationic lipids. J Biol Chem 280:12255–12261

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Ulrich AS (2002) Biophysical aspects of using liposomes as delivery vehicles. Biosci Rep 22:129–150

    PubMed  CAS  Google Scholar 

  • Wagner K, Harries D, May S, Kahl V, Rädler JO, Ben-Shaul A (2000) Direct evidence for counterion release upon cationic lipid-DNA condensation. Langmuir 16:303–306

    CAS  Google Scholar 

  • Walczyk D, Bombelli FB, Monopoli MP, Lynch I, Dawson KA (2010) What the cell “sees” in bionanoscience. J Am Chem Soc 132:5761–5768

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Wasungu L, Hoekstra D (2006) Cationic lipids, lipoplexes and intracellular delivery of genes. J Control Release 116:255–264

    PubMed  CAS  Google Scholar 

  • Woods NB, Bottero V, Schmidt M, Von Kalle C, Verma IM (2006) Gene therapy: therapeutic gene causing lymphoma. Nature 440:1123

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Zabner J, Fasbender AJ, Moninger T, Poellinger KA, Welsh MJ (1995) Cellular and molecular barriers to gene transfer by a cationic lipid. J Biol Chem 270:18997–19007

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Zuhorn IS, Hoekstra D (2002) On the mechanism of cationic amphiphile-mediated transfection. To fuse or not to fuse: is that the question? J Membr Biol 189:167–179

    PubMed  CAS  Google Scholar 

  • Zuhorn IS, Oberle V, Visser WH, Engberts JB, Bakowsky U, Polushkin E, Hoekstra D (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

    PubMed  CAS  Google Scholar 

  • Zuhorn IS, Bakowsky U, Polushkin E, Visser WH, Stuart MC, Engberts JB et al (2005) Nonbilayer phase of lipoplex-membrane mixture determines endosomal escape of genetic cargo and transfection efficiency. Mol Ther 11:801–810

    PubMed  CAS  Google Scholar 

  • Zuidam NJ, Barenholz Y (1997) Electrostatic parameters of cationic liposomes commonly used for gene delivery as determined by 4-heptadecyl-7-hydroxycoumarin. Biochim Biophys Acta 1329:211–222

    PubMed  CAS  Google Scholar 

  • Zuidam NJ, Barenholz Y (1998) Electrostatic and structural properties of complexes involving plasmid DNA and cationic lipids commonly used for gene delivery. Biochim Biophys Acta 1368:115–128

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to express gratitude to all their co-authors for collaborative efforts. A special acknowledge goes to Dr. Daniela Pozzi for her extraordinary work and support over the years.

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Authors and Affiliations

  1. Department of Molecular Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    Giulio Caracciolo

  2. Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Schmiedelstrasse 6, 8042, Graz, Austria

    Heinz Amenitsch

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  1. Giulio Caracciolo
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  2. Heinz Amenitsch
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Correspondence to Giulio Caracciolo.

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Special Issue: Scattering techniques in biology—Marking the contributions to the field from Peter Laggner on the occasion of his 68th birthday.

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Caracciolo, G., Amenitsch, H. Cationic liposome/DNA complexes: from structure to interactions with cellular membranes. Eur Biophys J 41, 815–829 (2012). https://doi.org/10.1007/s00249-012-0830-8

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  • DOI: https://doi.org/10.1007/s00249-012-0830-8

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