Journal of Molecular Medicine

, Volume 82, Issue 9, pp 579–591 | Cite as

Lipoplex-mediated delivery of nucleic acids: factors affecting in vivo transfection

Review

Abstract

For the past 15 years cationic liposomes have routinely been utilised for the delivery of nucleic acids such as plasmids and oligodeoxynucleotides to cells in culture and in vivo. These reagents are commercially available or are formulated inhouse. However, particularly in cultured cells, toxicity remains a significant problem, and this is confirmed by several in vivo findings. In addition, these complexes exhibit an immunostimulation effect, a phenomenon that may either be harmful or beneficial. Furthermore, lipoplexes have been recently found to have a certain degree of selectivity for dividing vascular endothelial cells. The development of cationic lipids that are safe to use especially in vivo and possess enhanced transfection capabilities is an ongoing process. More research is needed to understand the basic biology behind lipofection, first at the cellular level, then at the multicellular (whole organism) level.

Keywords

Cationic liposome Lipoplex Gene therapy Nucleic acid Delivery 

Abbreviations

CL

Cationic liposome

CLNAC

Cationic lipid–nucleic acid complex

CpG

Cytosine-phosphate-guanine

DC-chol

3β[N-(N’,N’-Dimethylaminoethan)-carbamoyl] cholesterol

DMRIE

3-Dimethyl-hydroxyethylammonium bromide

DOPE

Dioleoylphosphatidylethanolamine

DOTAP

N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate 1,2-dioleoyltrimethyl ammonium propane chloride

IFN

Interferon

IL

Interleukin

pDNA

Plasmid DNA

PEI

Polyethyleneimine

TNF

Tumor necrosis factor

VEC

Vascular endothelial cell

References

  1. 1.
    Felgner PL, Gadek TR, Holm M et al (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84:7413–7417Google Scholar
  2. 2.
    Choi JS, Lee EJ, Jang HS et al (2001) New cationic liposomes for gene transfer into mammalian cells with high efficiency and low toxicity. Bioconjug Chem 12:108–113CrossRefPubMedGoogle Scholar
  3. 3.
    Dass CR, Su T (2000) Delivery of lipoplexes for genotherapy of solid tumours: role of vascular endothelial cells. J Pharm Pharmacol 52:1301–1317PubMedGoogle Scholar
  4. 4.
    Wong FMP, Reimer DL, Bally MB (1996) Cationic lipid binding to DNA: characterization of complex formation. Biochemistry 35:5756–5763CrossRefPubMedGoogle Scholar
  5. 5.
    Liu F, Huang L (2002) Development of non-viral vectors for systemic gene delivery. J Control Release 78:259–266CrossRefPubMedGoogle Scholar
  6. 6.
    Felgner JH, Kumar R, Sridhar A et al (1994) Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations. J Biol Chem 269:2550–2561PubMedGoogle Scholar
  7. 7.
    Hafez IM, Maurer N, Cullis PR (2001) On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids. Gene Ther 8:1188–1196CrossRefPubMedGoogle Scholar
  8. 8.
    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 1368:115–128CrossRefPubMedGoogle Scholar
  9. 9.
    Dass CR (2002) Vehicles for oligonucleotide delivery: therapeutic applicability against tumors. J Pharm Pharmacol 54:3–27CrossRefPubMedGoogle Scholar
  10. 10.
    Lasic DD, Pearlman R (1996) Liposomes and lipidic particles in gene therapy. In: Rosoff M (ed) Vesicles. Dekker, New York, 477–489Google Scholar
  11. 11.
    Mui B, Ahkong QF, Chow L et al (2000) Membrane perturbation and the mechanism of lipid-mediated transfer of DNA into cells. Biochim Biophys Acta 1467:281–292CrossRefPubMedGoogle Scholar
  12. 12.
    Ren T, Song YK, Zhang G et al (2000) Structural basis of DOTMA for its high intravenous transfection activity in mouse. Gene Ther 7:764–768PubMedGoogle Scholar
  13. 13.
    Farhood H, Serbina N, Huang L (1995) The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer. Biochim Biophys Acta 1235:289–295CrossRefPubMedGoogle Scholar
  14. 14.
    Dass CR, Walker TL, Burton MA (2002) Liposomes containing cationic dimethyl dioctadecyl ammonium bromide: formulation, quality control, and lipofection efficiency. Drug Deliv 9:11–18CrossRefPubMedGoogle Scholar
  15. 15.
    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 93:11454–11459CrossRefPubMedGoogle Scholar
  16. 16.
    Dass CR, Walker TL, Kalle WHJ et al (2000) A microsphere-lipoplex (microplex) vector for targeted gene therapy of cancer. II. In vivo biodistribution study in a solid tumor model. Drug Deliv 7:15–20PubMedGoogle Scholar
  17. 17.
    Dass CR, Burton MA (2002) A model for evaluating selective delivery of plasmid DNA to tumours via the vasculature. Cancer Biother Radiopharm 17:501–505CrossRefPubMedGoogle Scholar
  18. 18.
    Dass CR, Burton MA (2003) Modified microplex vector enhances transfection of cells in culture while maintaining tumour-selective gene delivery in vivo. J Pharm Pharmacol 55:19–25PubMedGoogle Scholar
  19. 19.
    Cao A, Briane D, Coudert R et al (2000) Delivery and pathway in MCF7 cells of DNA vectorized by cationic liposomes derived from cholesterol. Antisense Nucleic Acid Drug Dev 10:369–380PubMedGoogle Scholar
  20. 20.
    Bell PC, Bergsma M, Dolbnya IP et al (2003) Transfection mediated by gemini surfactants: engineered escape from the endosomal compartment. J Am Chem Soc 125:1551–1558CrossRefPubMedGoogle Scholar
  21. 21.
    Friend DS, Papahadjopoulos D, Debs R (1996) Endocytosis and intracellular processing accompanying transfection mediated by cationic liposomes. Biochim Biophys Acta 1278:41–50CrossRefPubMedGoogle Scholar
  22. 22.
    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 84:3307–3316PubMedGoogle Scholar
  23. 23.
    Kreiss P, Cameron B, Rangara R et al (1999) Plasmid DNA size does not affect the physicochemical properties of lipoplexes but modulates gene transfer efficiency. Nucleic Acids Res 27:3792–3798CrossRefPubMedGoogle Scholar
  24. 24.
    Wu-Pong S, Weiss TL, Hunt CA (1992) Antisense c-myc oligodeoxyribonucleotide cellular uptake. Pharm Res 9:1010–1017CrossRefPubMedGoogle Scholar
  25. 25.
    Dass CR, Saravolac EG, Li Y et al (2002) Cellular uptake, distribution, and stability of 10–23 deoxyribozymes. Antisense Nucleic Acid Drug Dev 12:289–299CrossRefPubMedGoogle Scholar
  26. 26.
    Bielinska A, Kukowska-Latallo JF, Johnson J et al (1996) Regulation of in vitro gene expression using antisense oligonucleotides or antisense expression plasmids transfected using starburst PAMAM dendrimers. Nucleic Acids Res 24:2176–2182CrossRefPubMedGoogle Scholar
  27. 27.
    Lambert G, Fattal E, Brehier A et al (1998) Effect of polyisobutylcyanoacrylate nanoparticles and lipofectin loaded with oligonucleotides on cell viability and PKC alpha neosynthesis in HepG2 cells. Biochimie 80:969–976CrossRefPubMedGoogle Scholar
  28. 28.
    Xu M, Chen QR, Kumar D et al (1998) In vivo gene therapy with a cationic polymer markedly enhances the antitumor activity of antiangiogenic genes. Mol Genet Metab 64:193–197CrossRefPubMedGoogle Scholar
  29. 29.
    Lappalainen K, Jskeläinen I, Syrjänen J et al (1994) Comparison of cell proliferation and toxicity assays using two cationic liposomes. Pharm Res 11:1127–1131CrossRefPubMedGoogle Scholar
  30. 30.
    Aberle AM, Tablin F, Walker NJ et al (1998) A novel tetraester construct that reduces cationic lipid-associated cytotoxicity. Implications for the onset of cytotoxicity. Biochemistry 37:6533–6540CrossRefPubMedGoogle Scholar
  31. 31.
    Senior JH, Trimble KR, Maskiewicz R (1991) Interaction of positively-charged liposomes with blood: implications for their application in vivo. Biochim Biophys Acta 1070:173–179PubMedGoogle Scholar
  32. 32.
    Sakurai F, Nishioka T, Saito H et al (2001) Interaction between DNA-cationic liposome complexes and erythrocytes is an important factor in systemic gene transfer via the intravenous route in mice: the role of the neutral helper lipid. Gene Ther 8:677–686CrossRefPubMedGoogle Scholar
  33. 33.
    Ferencick M, Lacko I, Devinsky F (1990) Immunomodulatory activity of some amphiphilic compounds. Pharmazie 45:695–696PubMedGoogle Scholar
  34. 34.
    Jahnova E, Ferencick M, Nyulassy S et al (1994) Amphiphilic detergents inhibit production of IgG and IgM by human peripheral blood mononuclear cells. Immunol Lett 39:71–75CrossRefGoogle Scholar
  35. 35.
    Filion MC, Phillips NC (1997) Toxicity and immunomodulatory activity of some liposomal vectors formulated with cationic lipids toward immune effector cells. Biochim Biophys Acta 1329:345–356CrossRefPubMedGoogle Scholar
  36. 36.
    Pleyer U, Groth D, Hinz B et al (2001) Efficiency and toxicity of liposome-mediated gene transfer to corneal epithelial cells. Exp Eye Res 73:1–7CrossRefPubMedGoogle Scholar
  37. 37.
    Adams DO, Hamilton TA (1977) The cell biology of macrophage activation. Annu Rev Immunol 2:283–318CrossRefGoogle Scholar
  38. 38.
    Taniguchi K, Yamamoto Y, Itakura K et al (1988) Assessment of ocular irritability of liposome preparations. J Pharmacobiodyn 11:607–611PubMedGoogle Scholar
  39. 39.
    Chonn A, Cullis P, Devine D (1991) The role of surface charge in the activation of the classical and alternative pathways of complement by liposomes. J Immunol 146:4234–4241PubMedGoogle Scholar
  40. 40.
    Nita I, Ghivizzani SC, Galea-Lauri J et al (1996) Direct gene delivery to synovium. An evaluation of potential vectors in vitro and in vivo. Arthritis Rheum 39:820–828PubMedGoogle Scholar
  41. 41.
    Uyechi LS, Gagne L, Thurston G et al (2001) Mechanism of lipoplex gene delivery in mouse lung: binding and internalization of fluorescent lipid and DNA components. Gene Ther 8:828–836CrossRefPubMedGoogle Scholar
  42. 42.
    Malone RW (1995) Toxicology of non-viral gene transfer. In: Walsh B (ed) Non-viral genetic therapeutics: advances, challenges and applications for self-assembling systems. IBC Biomedical Library Series, Boston, 4.1.1–4.1.26Google Scholar
  43. 43.
    Freimark BD, Blezinger HP, Florack VJ et al (1998) Cationic lipids enhance cytokine and cell influx levels in the lung following administration of plasmid:cationic lipid complexes. J Immunol 160:4580–4586PubMedGoogle Scholar
  44. 44.
    Eliyahu H, Servel N, Domb AJ et al (2002) Lipoplex-induced hemagglutination: potential involvement in intravenous gene delivery. Gene Ther 9:850–858CrossRefPubMedGoogle Scholar
  45. 45.
    Barron LG, Meyer KB, Szoka FC Jr (1998) Effects of complement depletion on the pharmacokinetics and gene delivery mediated by cationic lipid-DNA complexes. Hum Gene Ther 9:315–923PubMedGoogle Scholar
  46. 46.
    Litzinger DC, Brown JM, Wala I et al (1996) Fate of cationic liposomes and their complex with oligonucleotide in vivo. Biochim Biophys Acta 1281:139–149CrossRefPubMedGoogle Scholar
  47. 47.
    Filion MC, Phillips NC (1997) Anti-inflammatory activity of cationic lipids. Br J Pharmacol 122:551–557PubMedGoogle Scholar
  48. 48.
    Wright MJ, Rosenthal E, Stewart L et al (1998) β-Galactosidase staining following intracoronary infusion of cationic liposomes in the in vivo rabbit heart is produced by microinfarction rather than effective gene transfer: a cautionary tale. Gene Ther 5:301–308CrossRefPubMedGoogle Scholar
  49. 49.
    Filion MC, Phillips NC (1998) Major limitations in the use of cationic liposomes for DNA delivery. Int J Pharm 162:159–170CrossRefGoogle Scholar
  50. 50.
    Madry H, Reszka R, Bohlender J et al (2001) Efficacy of cationic liposome-mediated gene transfer to mesangial cells in vitro and in vivo. J Mol Med 79:184–189CrossRefPubMedGoogle Scholar
  51. 51.
    Mohr L, Yoon SK, Eastman SJ et al (2001) Cationic liposome-mediated gene delivery to the liver and to hepatocellular carcinomas in mice. Hum Gene Ther 12:799–809Google Scholar
  52. 52.
    Dass CR (1998) Targeted delivery of DNA for therapy of cancer. Thesis, Charles Sturt University, Wagga Wagga, AustraliaGoogle Scholar
  53. 53.
    Minchin RF, Carpenter D, Orr RJ (2001) Polyinosinic acid and polycationic liposomes attenuate the hepatic clearance of circulating plasmid DNA. J Pharmacol Exp Ther 296:1006–1012PubMedGoogle Scholar
  54. 54.
    Dass CR (2002) Biochemical and biophysical characteristics of lipoplexes pertinent to solid tumour gene therapy. Int J Pharm 241:1–25CrossRefPubMedGoogle Scholar
  55. 55.
    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 45:99–114CrossRefPubMedGoogle Scholar
  56. 56.
    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 7:1701–1717PubMedGoogle Scholar
  57. 57.
    Bennett MJ, Aberle AM, Balasubramaniam S et al (1997) Cationic lipid-mediated gene delivery to murine lung: correlation of lipid hydration with in vivo transfection activity. J Med Chem 40:4069–4078CrossRefPubMedGoogle Scholar
  58. 58.
    Balasubramaniam RP, Bennett MJ, Aberle AM et al (1996) Structural and functional analysis of cationic transfection lipids: the hydrophobic domain. Gene Ther 3:163–3172PubMedGoogle Scholar
  59. 59.
    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 43:4617–4628CrossRefPubMedGoogle Scholar
  60. 60.
    van der Woude I, Wagenaar A, Meekel AA et al (1997) Novel pyridinium surfactants for efficient, nontoxic in vitro gene delivery. Proc Natl Acad Sci USA 94:1160–1165CrossRefPubMedGoogle Scholar
  61. 61.
    Tang F, Hughes JA (1999) Use of dithiodiglycolic acid as a tether for cationic lipids decreases the cytotoxicity and increases transgene expression of plasmid DNA in vitro. Bioconjug Chem 10:791–796CrossRefPubMedGoogle Scholar
  62. 62.
    Leventis R, Silvius JR (1990) Interactions of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. Biochim Biophys Acta 1023:124–132CrossRefPubMedGoogle Scholar
  63. 63.
    Farhood H, Bortega R, Epand RM et al (1992) Effect of cationic cholesterol derivatives on gene transfer and protein kinase C activity. Biochim Biophys Acta 1368:276–288Google Scholar
  64. 64.
    Ghosh YK, Visweswariah SS, Bhattacharya S (2000) Nature of linkage between the cationic headgroup and cholesteryl skeleton controls gene transfection efficiency. FEBS Lett 473:341–344CrossRefPubMedGoogle Scholar
  65. 65.
    Tang F, Hughes JA (1999) Synthesis of a single-tailed cationic lipid and investigation of its transfection. J Control Release 62:345–358CrossRefPubMedGoogle Scholar
  66. 66.
    Ferrari ME, Rusalov D, Enas J et al (2001) Trends in lipoplex physical properties dependent on cationic lipid structure, vehicle and complexation procedure do not correlate with biological activity. Nucleic Acids Res 29:1539–1548CrossRefPubMedGoogle Scholar
  67. 67.
    Floch V, Delepine P, Guillaume C et al (2000) Systemic administration of cationic phosphonolipid/DNA complexes and the relationship between formulation and lung transfection efficiency. Biochim Biophys Acta 1464:95–103CrossRefPubMedGoogle Scholar
  68. 68.
    Schuele RK, St. George JA, Bagley RG et al (1997) Basis of pulmonary toxicity associated with cationic lipid-mediated gene transfer to the mammalian lung. Hum Gene Ther 8:689–707PubMedGoogle Scholar
  69. 69.
    Li S, Wu SP, Whitmore M et al (1999) Effect of immune response on gene transfer to the lung via systemic administration of cationic lipidic vectors. Am J Physiol Lung Cell Mol Physiol 20 276:L796–L804Google Scholar
  70. 70.
    Dass CR, Burton MA (1999) Lipoplexes and tumors. J Pharm Pharmacol 51:755–770PubMedGoogle Scholar
  71. 71.
    Ozmen L, Pericin M, Hakimi J et al (1994) Interleukin 12, interferon γ, and tumor necrosis factor α are the key cytokines of the generalized Shwartzmann reaction. J Exp Med 180:907–915PubMedGoogle Scholar
  72. 72.
    Sparwasser T, Miethke T, Lipford G et al (1997) Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor-α-mediated shock. Eur J Immunol 27:1671–1679PubMedGoogle Scholar
  73. 73.
    Meyer O, Schugart K, Pavirani A et al (1999) Multiple systemic expression of human interferon-β in mice can be achieved upon repeated administration of optimized pcTG90-lipoplex. Gene Ther 7:1606–1611CrossRefGoogle Scholar
  74. 74.
    Yew NS, Wang KX, Przbylska M et al (1998) Contribution of plasmid DNA to inflammation in the lung after administration of cationic lipid:pDNA complexes. Hum Gene Ther 10:223–234CrossRefGoogle Scholar
  75. 75.
    Alton EWF, Geddes W, Gill DM et al (1998) Towards gene therapy for cystic fibrosis: a clinical progress report. Gene Ther 5:291–292PubMedGoogle Scholar
  76. 76.
    Schuele RK (2000) The role of CpG motifs in immunostimulation and gene therapy. Adv Drug Deliv Rev 44:119–134PubMedGoogle Scholar
  77. 77.
    Yew NS, Zhao H, Wu IH et al (2000) Reduced inflammatory response to plasmid vectors by elimination and inhibition of immunostimulatory CpG motifs. Mol Ther 1:255–262CrossRefPubMedGoogle Scholar
  78. 78.
    Tan Y, Li S, Pitt BR et al (1999) The inhibitory role of CpG immunostimulatory motifs in cationic lipid vector-mediated transgene expression in vivo. Hum Gene Ther 10:2153–2161CrossRefPubMedGoogle Scholar
  79. 79.
    Qin L, Ding Y, Pahud DR et al (1997) Promoter attenuation in gene therapy: interferon-γ and tumor necrosis factor-α inhibit transgene expression. Hum Gene Ther 8:2019–2029PubMedGoogle Scholar
  80. 80.
    Dow SW, Fradkin LG, Liggitt DH et al (1999) Lipid-DNA complexes induce potent activation of innate immune responses and antitumor activity when administered intravenously. J Immunol 163:1552–1561PubMedGoogle Scholar
  81. 81.
    Whitmore M, Li S, Huang L (1999) LPD lipoployplex initiates a potent cytokine response and inhibits tumor growth. Gene Ther 6:1867–1875PubMedGoogle Scholar
  82. 82.
    Bramson JL, Bodner CA, Graham RW (2000) Activation of host tumoral responses by cationic lipid/DNA complexes. Cancer Gene Ther 7:353–359PubMedGoogle Scholar
  83. 83.
    Loisel S, Le Gall C, Doucet L et al (2001) Contribution of plasmid DNA to hepatotoxicity after systemic administration of lipoplexes. Hum Gene Ther 12:685–696CrossRefPubMedGoogle Scholar
  84. 84.
    Parker SE, Khatibi S, Margalith M et al (1996) Plasmid DNA gene therapy: studies with the human interleukin-12 gene in tumor cells in vitro and in the murine B16 model in vivo. Cancer Gene Ther 3:175–185PubMedGoogle Scholar
  85. 85.
    Blezinger P, Freimark BD, Matar M et al (1999) Intratracheal administration of interleukin 12 plasmid-cationic lipid complexes inhibits murine lung metastases. Hum Gene Ther 10:723–731PubMedGoogle Scholar
  86. 86.
    Dow SW, Elmslie RE, Fradkin LG et al (1999) Intravenous cytokine gene delivery by lipid-DNA complexes controls the growth of established lung metastases. Hum Gene Ther 10:2961–2972CrossRefPubMedGoogle Scholar
  87. 87.
    Lanuti M, Rudginsky S, Force SD et al (2000) Cationic lipid:bacterial DNA complexes elicit adaptive cellular immunity in murine intraperitoneal models. Cancer Res 60:2955–2963PubMedGoogle Scholar
  88. 88.
    Duda DG, Sunamura M, Lozonschi L et al (2000) Direct in vitro evidence and in vivo analysis of the antiangiogenesis effects of interleukin 12. Cancer Res 60:1111–1116PubMedGoogle Scholar
  89. 89.
    Strieter RM, Polverini PJ, Arenberg DA et al (1995) The role of CXC chemokines as regulators of angiogenesis. Shock 4:155–160PubMedGoogle Scholar
  90. 90.
    Perrie Y, Frederik PM, Gregoriadis G (2001) Liposome-mediated DNA vaccination: the effect of vesicle composition. Vaccine 19:3301–3310CrossRefPubMedGoogle Scholar
  91. 91.
    Reyes L, Hartikka J, Bozoukova V et al (2001) Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization. Vaccine 19:3778–3786PubMedGoogle Scholar
  92. 92.
    Neckers LM, Kanekal M, Connell Y (1998) Non-antisense oligonucleotide approaches for experimental treatment of glioblastoma. Antisense Nucl Acid Drug Dev 8:177–179Google Scholar
  93. 93.
    Mui B, Raney SG, Semple SC et al (2001) Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when encapsulated and delivered in lipid particles. J Pharmacol Exp Ther 298:1185–1192PubMedGoogle Scholar
  94. 94.
    Thurston G, McLean JW, Rizen M et al (1998) Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice. J Clin Invest 101:1401–1413PubMedGoogle Scholar
  95. 95.
    Campbell RB, Fukumura D, Brown EB et al (2002) Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. Cancer Res 62:6831–6836PubMedGoogle Scholar
  96. 96.
    Vincent S, DePace D, Finkelstein S (1988) Distribution of anionic sites on the capillary endothelium in an experimental brain tumour model. Microcirc Endothelium Lymphatics 4:45–67PubMedGoogle Scholar
  97. 97.
    Mounkes LC, Zhong W, Cipres-Palacin G et al (1998) Proteoglycans mediate cationic liposome-DNA complex-based gene delivery in vitro and in vivo. J Biol Chem 273:26164–26170CrossRefPubMedGoogle Scholar
  98. 98.
    Chang YS, di Tomaso E, McDonald DM et al (2000) Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci USA 97:14608–14613CrossRefPubMedGoogle Scholar
  99. 99.
    Bankston PW, Milici AJ (1983) A survey of the binding of polycationic ferritin in several fenestrated capillary beds: indication of heterogeneity in the luminal glycocalyx of fenestral diaphragms. Microvasc Res 26:36–48CrossRefPubMedGoogle Scholar
  100. 100.
    Milici AJ, L’Hernault N, Palade GE (1985) Surface densities of diaphragmed fenestrae and transendothelial channels in different murine capillary beds. Circ Res 56:709–717PubMedGoogle Scholar
  101. 101.
    Kerbel RS, Klement G, Pritchard KI et al (2002) Continuous low-dose anti-angiogenic/ metronomic chemotherapy: from the research laboratory into the oncology clinic. Ann Oncol 13:12–15Google Scholar
  102. 102.
    McLean JW, Fox EA, Baluk P et al (1997) Organ-specific endothelial cell uptake of cationic liposome-DNA complexes in mice. Am J Physiol 273:H387–H404PubMedGoogle Scholar
  103. 103.
    Kunstfeld R, Wickenhauser G, Michaelis U et al (2003) Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a “humanized” SCID mouse model. J Invest Dermatol 120:476–482CrossRefPubMedGoogle Scholar
  104. 104.
    Aoki K, Yoshida T, Matsumoto N et al (1997) Gene therapy for peritoneal dissemination of pancreatic cancer by liposome-mediated transfer of herpes simplex virus thymidine kinase gene. Hum Gene Ther 8:1105–1113PubMedGoogle Scholar
  105. 105.
    Kikuchi A, Aoki Y, Sugaya S et al (1999) Development of novel cationic liposomes for efficient gene transfer into peritoneal disseminated tumor. Hum Gene Ther 10:947–955CrossRefPubMedGoogle Scholar
  106. 106.
    Reddy JA, Abburi C, Hofland SJ et al (2002) Folate-targeted, cationic liposome-mediated gene transfer into disseminated peritoneal tumors. Gene Ther 9:1542–1550CrossRefPubMedGoogle Scholar
  107. 107.
    Kiyasu Y, Kaneshima S, Koga S (1981) Morphogenesis of peritoneal metastasis in human gastric cancer. Cancer Res 41:1236–1239PubMedGoogle Scholar
  108. 108.
    Niedbala MJ, Crickard K, Bernacki RJ (1985) Interactions of human ovarian tumor cells with human mesothelial cells grown on extracellular matrix. An in vitro model system for studying tumor cell adhesion and invasion. Exp Cell Res 160:499–513PubMedGoogle Scholar
  109. 109.
    Parker SE, Ducharme S, Norman J et al (1997) Tissue distribution of the cytofectin component of a plasmid-DNA/cationic lipid complex following intravenous administration in mice. Hum Gene Ther 8:393–401PubMedGoogle Scholar
  110. 110.
    Niven R, Pearlman R, Wedeking T et al (1998) Biodistribution of radiolabeled lipid-DNA complexes and DNA in mice. J Pharm Sci 87:1292–1299CrossRefPubMedGoogle Scholar
  111. 111.
    Audouy SA, de Leij LF, Hoekstra D et al (2002) In vivo characteristics of cationic liposomes as delivery vectors for gene therapy. Pharm Res 9:1599–1605CrossRefGoogle Scholar
  112. 112.
    Ramesh R, Saeki T, Templeton NS et al (2001) Successful treatment of primary and disseminated human lung cancers by systemic delivery of tumor suppressor genes using an improved liposome vector. Mol Ther 3:337–344CrossRefPubMedGoogle Scholar
  113. 113.
    Liu Y, Mounkes LC, Liggitt HD et al (1997) Factors influencing the efficiency of cationic liposome-mediated intravenous gene delivery. Nat Biotechnol 15:167–173PubMedGoogle Scholar
  114. 114.
    Sakurai F, Terada T, Yasuda K et al (2002) The role of tissue macrophages in the induction of proinflammatory cytokine production following intravenous injection of lipoplexes. Gene Ther 9:1120–1126CrossRefPubMedGoogle Scholar
  115. 115.
    Rainov NG, Ikeda K, Qureshi NH et al (1999) Intraarterial delivery of adenovirus vectors and liposome-DNA complexes to experimental brain neoplasms. Hum Gene Ther 10:311–318CrossRefPubMedGoogle Scholar
  116. 116.
    Zhu N, Liggitt D, Liu Y et al (1993) Systemic gene expression after intravenous DNA delivery into adult mice. Science 261:209–211PubMedGoogle Scholar
  117. 117.
    Templeton NS, Lasic DD, Frederik PM et al (1997) Improved DNA liposome complexes for increased systemic delivery and gene expression. Nat Biotechnol 15:647–652PubMedGoogle Scholar
  118. 118.
    Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279:377–380PubMedGoogle Scholar
  119. 119.
    Arap W, Haedicke W, Bernasconi M et al (2002) Targeting the prostate for destruction through a vascular address. Proc Natl Acad Sci USA 99:1527–1531CrossRefPubMedGoogle Scholar
  120. 120.
    Nabel GJ, Nabel EG, Yang ZY, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE (1993) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci USA 90:11307–11311PubMedGoogle Scholar
  121. 121.
    Nabel EG, Yang Z, Muller D, Chang AE, Gao X, Huang L, Cho KJ, Nabel GJ (1994) Safety and toxicity of catheter gene delivery to the pulmonary vasculature in a patient with metastatic melanoma. Hum Gene Ther 5:1089–1094PubMedGoogle Scholar
  122. 122.
    Sorscher EJ, Logan JJ, Frizzell RA, Lyrene RK, Bebok Z, Dong JY, Duvall MD, Felgner PL, Matalon S, Walker L et al. (1994) Gene therapy for cystic fibrosis using cationic liposome mediated gene transfer: a phase I trial of safety and efficacy in the nasal airway. Hum Gene Ther 5:1259–1277PubMedGoogle Scholar
  123. 123.
    Xing X, Yujiao Chang J, Hung M (1998) Preclinical and clinical study of HER-2/neu-targeting cancer gene therapy. Adv Drug Deliv Rev 30:219–227CrossRefPubMedGoogle Scholar
  124. 124.
    Hortobagyi GN, Ueno NT, Xia W, Zhang S, Wolf JK, Putnam JB, Weiden PL, Willey JS, Carey M, Branham DL, Payne JY, Tucker SD, Bartholomeusz C, Kilbourn RG, De Jager RL, Sneige N, Katz RL, Anklesaria P, Ibrahim NK, Murray JL, Theriault RL, Valero V, Gershenson DM, Bevers MW, Huang L, Lopez-Berestein G, Hung MC (2001) Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial. J Clin Oncol 19:3422–3433PubMedGoogle Scholar
  125. 125.
    Ruiz FE, Clancy JP, Perricone MA, Bebok Z, Hong JS, Cheng SH, Meeker DP, Young KR, Schoumacher RA, Weatherly MR, Wing L, Morris JE, Sindel L, Rosenberg M, van Ginkel FW, McGhee JR, Kelly D, Lyrene RK, Sorscher EJ (2001) A clinical inflammatory syndrome attributable to aerosolized lipid-DNA administration in cystic fibrosis. Hum Gene Ther 12:751–761PubMedGoogle Scholar
  126. 126.
    Yoshida J, Mizuno M, Fujii M, Kajita Y, Nakahara N, Hatano M, Saito R, Nobayashi M, Wakabayashi T (2004) Human gene therapy for malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) by in vivo transduction with human interferon beta gene using cationic liposomes. Hum Gene Ther 15:77–86CrossRefPubMedGoogle Scholar
  127. 127.
    Caplen NJ, Alton EW, Middleton PG, Dorin JR, Stevenson BJ, Gao X, Durham SR, Jeffery PK, Hodson ME, Coutelle C et al. (1995) Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nat Med 1:39–46PubMedGoogle Scholar
  128. 128.
    Hui KM, Ang PT, Huang L, Tay SK (1997) Phase I study of immunotherapy of cutaneous metastases of human carcinoma using allogeneic and xenogeneic MHC DNA-liposome complexes. Gene Ther 4:783–790PubMedGoogle Scholar
  129. 129.
    Gill DR, Southern KW, Mofford KA, Seddon T, Huang L, Sorgi F, Thomson A, MacVinish LJ, Ratcliff R, Bilton D, Lane DJ, Littlewood JM, Webb AK, Middleton PG, Colledge WH, Cuthbert AW, Evans MJ, Higgins CF, Hyde SC (1997) A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther 4:199–209PubMedGoogle Scholar
  130. 130.
    Noone PG, Hohneker KW, Zhou Z, Johnson LG, Foy C, Gipson C, Jones K, Noah TL, Leigh MW, Schwartzbach C, Efthimiou J, Pearlman R, Boucher RC, Knowles MR (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 1:105–114CrossRefPubMedGoogle Scholar
  131. 131.
    Hyde SC, Southern KW, Gileadi U, Fitzjohn EM, Mofford KA, Waddell BE, Gooi HC, Goddard CA, Hannavy K, Smyth SE, Egan JJ, Sorgi FL, Huang L, Cuthbert AW, Evans MJ, Colledge WH, Higgins CF, Webb AK, Gill DR (2000) Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis. Gene Ther 7:1156–1165CrossRefPubMedGoogle Scholar
  132. 132.
    Ren H, Boulikas T, Lundstrom K, Soling A, Warnke PC, Rainov NG (2003) Immunogene therapy of recurrent glioblastoma multiforme with a liposomally encapsulated replication-incompetent Semliki forest virus vector carrying the human interleukin-12 gene-a phase I/II clinical protocol. J Neurooncol 64:147–154CrossRefPubMedGoogle Scholar
  133. 133.
    Nabel GJ, Gordon D, Bishop DK, Nickoloff BJ, Yang ZY, Aruga A, Cameron MJ, Nabel EG, Chang AE (1996) Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA-liposome complexes. Proc Natl Acad Sci USA 93:15388–15393PubMedGoogle Scholar
  134. 134.
    Porteous DJ, Dorin JR, McLachlan G, Davidson-Smith H, Davidson H, Stevenson BJ, Carothers AD, Wallace WA, Moralee S, Hoenes C, Kallmeyer G, Michaelis U, Naujoks K, Ho LP, Samways JM, Imrie M, Greening AP, Innes JA (1997) Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther 4:210–218CrossRefPubMedGoogle Scholar
  135. 135.
    Brigham KL, Lane KB, Meyrick B, Stecenko AA, Strack S, Cannon DR, Caudill M, Canonico AE (2000) Transfection of nasal mucosa with a normal alpha1-antitrypsin gene in alpha1-antitrypsin-deficient subjects: comparison with protein therapy. Hum Gene Ther 11:1023–1032CrossRefPubMedGoogle Scholar
  136. 136.
    Stopeck AT, Jones A, Hersh EM, Thompson JA, Finucane DM, Gutheil JC, Gonzalez R (2001) Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/beta2-microglobulin DNA-liposome complex, in patients with metastatic melanoma. Clin Cancer Res 7:2285–2291PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.GeneType Research Labs.FitzroyAustralia

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