Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

Novel gene delivery systems: complexes of fusigenic polymer-modified liposomes and lipoplexes

Gene Therapy volume 8, pages 5–12 (2001)Cite this article

Abstract

We have previously developed the succinylated poly(glycidol)-modified liposome which becomes fusigenic under weakly acidic condition. In this report, we describe that complexation of this pH-sensitive, fusigenic liposome with a lipoplex consisting of 3β-(N-(N′,N′-dimethylaminoethane) carbamoyl)cholesterol, dioleoylphosphatidylethanolamine and plasmid DNA gives efficient gene delivery systems. In this study, we prepared the complexes, which are termed SucPG-complexes, with a positively or negatively charged surface by mixing the lipoplex with varying amounts of the SucPG-modified liposomes. The positively charged SucPG-complexes either bearing or not bearing a cell-specific ligand, transferrin, could transfect HeLa cells efficiently. In contrast, the negatively charged complexes hardly transfected the cells when transferrin was not conjugated to them. However, the negatively charged SucPG complexes bearing transferrin exhibited high transfection ability against HeLa and K562 cells, indicating that this gene delivery was achieved through their binding to the cellular receptors. These transferrin-attached, negatively charged complexes retained the high transfection ability in the presence of serum. Thus, this negatively charged complex may be useful as nonviral vectors in vivo.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Behr JP . Synthetic gene-transfer vectors Acc Chem Res 1993 26: 274–278

    Article  CAS  Google Scholar 

  2. Pouton CW, Seymour LW . Key issues in non-viral gene delivery Adv Drug Del Rev 1998 34: 3–19

    Article  CAS  Google Scholar 

  3. Felgner PL . Particulate systems and polymers for in vitro and in vivo delivery of polynucleotides Adv Drug Del Rev 1990 5: 163–187

    Article  CAS  Google Scholar 

  4. Singhal A, Huang L . Gene transfer in mammalian cells using liposomes as carriers. In: Wolf JA (ed) Gene Therapeutics Birkhäuser: Boston 1993 118–142

    Google Scholar 

  5. Lasic D . Liposomes in Gene Delivery CRC Press: Boca Raton 1997

    Google Scholar 

  6. Chonn A, Cullis PR . Recent advances in liposome technologies and their applications for systemic gene delivery Adv Drug Del Rev 1998 30: 73–83

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Felgner PL et al. Nomenclature for synthetic gene delivery systems Hum Gene Ther 1997 8: 511–512

    Article  CAS  Google Scholar 

  9. Felgner PL et al. Lipofection: a highly efficient, lipid-mediated DNA transfection procedure Proc Natl Acad Sci USA 1987 84: 7413–7414

    Article  CAS  Google Scholar 

  10. Mönkkönen J, Urtti A . Lipid fusion in oligonucleotide and gene delivery with cationic lipids Adv Drug Del Rev 1998 34: 37–49

    Article  Google Scholar 

  11. Wrobel I, Collins D . Fusion of cationic liposomes with mammalian cells occurs after endocytosis Biochim Biophys Acta 1995 1235: 296–304

    Article  Google Scholar 

  12. Zhou X, Huang L . DNA transfection mediated by cationic liposomes containing lipopolylysine: characterization and mechanism of action Biochim Biophys Acta 1994 1189: 195–203

    Article  CAS  Google Scholar 

  13. Friend DS, Papahadjopoulos D, Debs RJ . Endocytosis and intracellular processing accompanying transfection mediated by cationic liposomes Biochim Biophys Acta 1996 1278: 41–50

    Article  Google Scholar 

  14. Zabner J et al. Cellular and molecular barriers to gene transfer by a cationic lipid J Biol Chem 1995 270: 18997–19007

    Article  CAS  Google Scholar 

  15. Wagner E . Application of membrane-active peptides for nonviral gene delivery Adv Drug Del Rev 1999 38: 279–289

    Article  CAS  Google Scholar 

  16. Kamata H, Yagisawa H, Takahashi S, Hirata H . Amphiphilic peptides enhance the efficiency of liposome-mediated DNA transfection Nucleic Acids Res 1994 22: 536–537

    Article  CAS  Google Scholar 

  17. Kichler A, Mechtler K, Behr JP, Wagner E . Influence of membrane-active peptides on lipospermine/DNA complex mediated gene transfer Bioconj Chem 1997 8: 213–221

    Article  CAS  Google Scholar 

  18. Simoes S et al. Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusogenic peptides Gene Therapy 1998 5: 955–964

    Article  CAS  Google Scholar 

  19. Kono K, Zenitani K, Takagishi T . Novel pH-sensitive liposomes: liposomes bearing a poly(ethylene glycol) derivatives Biochim Biophys Acta 1994 1193: 1–9

    Article  CAS  Google Scholar 

  20. Kono K, Igawa T, Takagishi T . Cytoplasmic delivery mediated by liposomes modified with a pH-sensitive poly(ethylene glycol) derivative Biochim Biophys Acta 1997 1325: 143–154

    Article  CAS  Google Scholar 

  21. Forssen E, Wilis M . Ligand-targeted liposomes Adv Drug Del Rev 1998 29: 249–271

    Article  CAS  Google Scholar 

  22. Aisen P . Iron transport and strage proteins Ann Rev Biochem 1980 49: 357–393

    Article  CAS  Google Scholar 

  23. Wagner E, Curiel D, Cotten M . Delivery of drugs, proteins and genes into cells using transferrin as a ligand for receptor-mediated endocytosis Adv Drug Del Rev 1994 14: 113–135

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Zhou X, Klibanov AL, Huang L . Lipophilic polylysines mediate efficient DNA transfection in mammalian cells Biochim Biophys Acta 1991 1065: 8–14

    Article  CAS  Google Scholar 

  26. Zelphati O, Uyechi LS, Barron LG, Szoka Jr FC . Effect of serum components on the physico-chemical properties of cationic lipid/oligonucleotide complexes and their interactions with cells Biochim Biophys Acta 1998 1390: 119–133

    Article  CAS  Google Scholar 

  27. Senior JH, Trimble KR, Maskiewicz R . Interaction of positively charged liposomes with blood: implications for their application in vivo Biochim Biophys Acta 1991 1070: 173–179

    Article  CAS  Google Scholar 

  28. Escriou V et al. Cationic lipid-mediated gene transfer: effect of serum on cellular uptake and intracellula fate of lipopolyamine/DNA complexes Biochim Biophys Acta 1998 1368: 276–288

    Article  CAS  Google Scholar 

  29. Sternberg B, Sorgi FL, Huang L . New structures in complex formation between DNA and cationic liposomes visualized by freeze–fracture electron microscopy FEBS Lett 1994 356: 361–366

    Article  CAS  Google Scholar 

  30. Yang J-P, Huang L . Time-dependent maturation of cationic liposome–DNA complex for serum resistance Gene Therapy 1998 5: 380–387

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  32. Wang CY, Huang L . Highly efficient DNA delivery mediated by pH-sensitive immunoliposomes Biochemistry 1989 28: 9508–9514

    Article  CAS  Google Scholar 

  33. Wang CY, Huang L . pH-sensitive immunoliposomes mediate target-cell-specific delivery and controlled expression of a foreign gene in mouse Proc Natl Acad Sci USA 1987 84: 7851–7855

    Article  CAS  Google Scholar 

  34. Lee RJ, Huang L . Folate-targeted, anionic liposome-entrapped polylysine-condensed DNA for tumor cell-specific gene transfer J Biol Chem 1996 271: 8481–8487

    Article  CAS  Google Scholar 

  35. Tros de Ilarduya C, Düzgünes N . Efficient gene transfer by transferrin lipoplexes in the presence of serum Biochim Biophys Acta 2000 1463: 333–342

    Article  CAS  Google Scholar 

  36. Gao X, Huang L . Potentiation of cationic liposome-mediated gene delivery by polycations Biochemistry 1996 35: 1027–1036

    Article  CAS  Google Scholar 

  37. Chalfie M et al. Green fluorescent protein as a marker for gene expression Science 1994 263: 802–805

    Article  CAS  Google Scholar 

  38. Struck DK, Hoekstra D, Pagano RE . Use of resonance energy transfer to monitor membrane fusion Biochemistry 1981 20: 4093–4099

    Article  CAS  Google Scholar 

  39. Kono K, Kimura S, Imanishi Y . pH-dependent interaction of amphiphilic polypeptide poly(Lys-Aib-Leu-Aib) with lipid bilayer membrane Biochemistry 1990 29: 3631–3637

    Article  CAS  Google Scholar 

  40. Kono K, Henmi A, Takagishi T . Temperature-controlled interaction of thermosensitive polymer-modified cationic liposomes with negatively charged phospholipid membranes Biochim Biophys Acta 1999 1421: 183–197

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was partly supported by the Grant-in-Aid from Japanese Ministry of Education, Science and Culture, and Terumo Life Science.

Author information

Authors and Affiliations

  1. Department of Applied Materials Science, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan

    K Kono, Y Torikoshi, M Mitsutomi & T Takagishi

  2. Department of Applied Bioscience, Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai, Osaka, Japan

    K Kono & T Takagishi

  3. First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Aichi, Japan

    T Itoh & N Emi

  4. Department of Surgery, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    H Yanagie

Authors
  1. K Kono
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Torikoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Mitsutomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Emi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Yanagie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Takagishi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kono, K., Torikoshi, Y., Mitsutomi, M. et al. Novel gene delivery systems: complexes of fusigenic polymer-modified liposomes and lipoplexes. Gene Ther 8, 5–12 (2001). https://doi.org/10.1038/sj.gt.3301365

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3301365

Keywords

This article is cited by

Search

Advanced search

Quick links