Liposomes as Macromolecular Carriers for the Introduction of RNA and DNA into Cells

  • D. Papahadjopoulos
  • T. Wilson
  • R. Taber
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 31)


Liposomes are vesicles composed of one or more lipid bilayers completely surrounding an internal aqueous space. They are usually composed of phospholipids either in pure form or in combination with other amphipathic molecules such as sterols, long chain bases or acids. The structure of liposomes varies from large (0.5 to 5μ) multilamellar vesicles (1) to small (~300Å) unilamellar vesicles (2, 3) or to unilamellar vesicles of intermediate size (4–6).


Lipid Vesicle Effective Delivery Phospholipid Vesicle Multilamellar Vesicle Specific Infectivity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1).
    Bangham, A.D., Standish, M.M. and Watkins, J.C. (1965). Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol., 13, 238.PubMedCrossRefGoogle Scholar
  2. 2).
    Papahadjopoulos, D. and Miller, N. (1967). Phospholipid model membranes. I. Structural characteristics of hydrated liquid crystals. Biochim. Biophys. Acta, 135, 624.PubMedCrossRefGoogle Scholar
  3. 3).
    Huang, C.H. (1969). Studies on phosphatidylcholine vesicles. Formation and physical characteristics. Biochem., 8, 344.CrossRefGoogle Scholar
  4. 4).
    Papahadjopoulos, D., Vail, W.J., Jacobson, K. and Poste, G. (1975). Cochleate lipid cylinders: Formation by fusion of unilamellar lipid vesicles. Biochim. Biophys. Acta, 394, 483.PubMedCrossRefGoogle Scholar
  5. 5).
    Deamer, D. and Bangham, A.D. (1976). Large volume liposomes by an ether evaporization method. Biochim. Biophys. Acta, 443, 629.PubMedCrossRefGoogle Scholar
  6. 6).
    Szoka, F. and Papahadjopoulos, D. (1978). A new procedure for preparation of liposomes with large internal aqueous space and high capture, by reverse phase evaporation (REV). Proc. Natl. Acad. Sci. USA, 75, 4194.PubMedCrossRefGoogle Scholar
  7. 7).
    Papahadjopoulos, D. and Kimelberg, H.K. (1973). Phospholipid vesicles (liposomes) as models for biological membranes. In: Progress in Surface Science (ed. S.G. Davison), 4, 141, Pergamon Press.Google Scholar
  8. 8).
    Bangham, A.D., Hill, M.W. and Miller, N.G.A. (1974). Preparation and use of liposomes as models of biological membranes. In: Methods in Membrane Biology (ed., E.D. Korn), 1, 1, Ch. 1, Plenum Press.Google Scholar
  9. 9).
    Gregoriadis, G. (1976). The carrier potential of liposomes in biology and medicine, New Eng. Journ. Med., 295, 704, 705.CrossRefGoogle Scholar
  10. 10).
    Poste, G., Papahadjopoulos, D. and Vail, W.J. (1976). Lipid vesicles as carriers for introducing biologically active materials into cells. In: Methods in Cell Biology (ed., D.M. Prescott), 14, 33, Academic Press, New York.Google Scholar
  11. 11).
    Tyrell, D.A., Heath, T.D., Colley, C.M. and Ryman, B.E. (1976). New aspects of liposomes. Biochim. Biophys. Acta, 457, 259.Google Scholar
  12. 12).
    Pagano, R.E. and Weinstein, J.N. (1978). Interactions of phospholipid vesicles with mammalian cells. Ann. Rev. Biophys. Bioengin., 7, 435.CrossRefGoogle Scholar
  13. 13).
    Kimbelberg, H.K. and Mayhew, E. (1979). Properties and biological effects of liposomes and their uses in pharmacology and toxicology. Crit. Revs. Toxicol., 6, 25.CrossRefGoogle Scholar
  14. 14).
    Papahadjopoulos, D. (1978). Liposomes and their uses in biology and medicine. Ann. N.Y. Acad. Sci., 308, 1.CrossRefGoogle Scholar
  15. 15).
    Batzri, S. and Korn, E.D. (1973). Single bilayer liposomes prepared without sonication. Biochim. Biophys. Acta, 298, 1015.PubMedCrossRefGoogle Scholar
  16. 16).
    Kremer, J.M.H., Esker, J., Pathmamanoharan, C. and Wiersema, P.H. (1977). Vesicles of variable diameter prepared by a modified injection method. Biochem., 16, 3932.CrossRefGoogle Scholar
  17. 17).
    Szoka, F. and Papahadjopoulos, D. (1980). Comparative properties and methods of preparation of lipid vesicles (liposomes). Ann. Rev. Biophys. Bioengin., in press.Google Scholar
  18. 18).
    Wilson, T., Papahadjopoulos, D. and Taber, R. (1977). Biological properties of poliovirus encapsulated in lipid vesicles: antibody resistance and infectivity in virus-resistant cells. Proc. Natl. Acad. Sci. USA, 74, 3471.PubMedCrossRefGoogle Scholar
  19. 19).
    Wilson, T., Papahadjopoulos, D. and Taber, R. (1979). The introduction of poliovirus RNA into cells via lipid vesicles (liposomes). Cell, 17, 77.PubMedCrossRefGoogle Scholar
  20. 20).
    Olson, F., Hunt, C.A., Szoka, F.C, Vail, W.J. and Papahadjopoulos, D. (1979). Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes. Biochem. Biophys. Acta, in press.Google Scholar
  21. 21).
    Poste, G. and Papahadjopoulos, D. (1978). The influence of vesicle membrane properties on the interaction of lipid vesicles with cultured cells. Ann. N.Y. Acad. Sci., 308, 164.PubMedCrossRefGoogle Scholar
  22. 22).
    Papahadjopoulos, D., Mayhew, E., Poste, G., Smith, S. and Vail, W.J. (1974). Incorporation of lipid vesicles by mammalian cells provides a potential method for modifying cell behavior. Nature, 252, 163.PubMedCrossRefGoogle Scholar
  23. 23).
    Pagano, R.E. and Huang, L. (1975). Interactions of phospholipid vesicles with mammalian cells. II. Studies of Mechanism. J. Cell Biol., 67, 49.PubMedCrossRefGoogle Scholar
  24. 24).
    Poste, G. and Papahadjopoulos, D. (1976). Lipid vesicles as carriers for introducing materials into cultured cells: Influence of vesicle lipid composition on the mechanism of vesicle incorporation into cells. Proc. Natl. Acad. Sci., 73, 1603.PubMedCrossRefGoogle Scholar
  25. 25).
    Martin, F.J. and Macdonald, R.C. (1976). Lipid vesicle-cell interactions. II. Introduction of cell fusion. J. Cell. Biol., 70, 506.PubMedCrossRefGoogle Scholar
  26. 26).
    Martin, F.J. and Macdonald, R.C. (1976). Lipid vesicle-cell interactions. III. Introduction of a new antigenic determinant into erythrocyte membranes. J. Cell Biol., 70, 515.PubMedCrossRefGoogle Scholar
  27. 27).
    Weissmann, G., Cohen, C. and Hoffstein, S. (1977). Introduction of enzymes, by means of liposomes, into non-phagocytic human cells in vitro. Biochim. Biophys. Acta, 498, 375.PubMedCrossRefGoogle Scholar
  28. 28).
    Schroit, A.J. and Pagano, R.E. (1978). Introduction of antigenic phospholipids into the plasma membrane of mammalian cells: Organization and antibody-induced lipid redistribution. Proc. Natl. Acad. Sci., 75, 5529.PubMedCrossRefGoogle Scholar
  29. 29).
    Batzri, S. and Korn, E.D. (1975). Interaction of phospholipid vesicles with cells. Endocytosis and fusion as alternate mechanisms for the uptake of lipid-soluble and water-soluble molecules. J. Cell Biol., 66, 621.PubMedCrossRefGoogle Scholar
  30. 30).
    Cohen, C.M., Weissmann, G., Hoffstein, S., Awasthi, U.C. and Srivastava, S.K. (1976). Introduction of purified hexosaminidase A into Tay-Sachs leukocytes by means of immunoglobulincoated liposomes. Biochem., 15, 452.CrossRefGoogle Scholar
  31. 31).
    Pagano, R.E. and Takeichi, M. (1977). Adhesion of phospholipid vesicles to Chinese hamster fibroblasts: role of serum proteins. J. Cell Biol., 74, 531.PubMedCrossRefGoogle Scholar
  32. 32).
    Szoka, F., Jacobson, K. and Derzko, Z. (1978). Phospholipid vesicle-cell interactions studied by fluorescence techniques. Ann. N.Y. Acad. Sci., 308, 437.Google Scholar
  33. 33).
    Pagano, R.E., Sandra, A. and Takeichi, M. (1978). Interactions of phospholipid vesicles with mammalian cells. Ann. N.Y. Acad., 308, 185.CrossRefGoogle Scholar
  34. 34).
    Koch, G. and Bishop, J.N. (1968). The effect of polycation on the interaction of viral RNA with mammalian cells: studies on the infectivity of single-and double-stranded poliovirus RNA. Virology, 35, 9.PubMedCrossRefGoogle Scholar
  35. 35).
    Szoka, F., Jacobson, K. and Papahadjopoulos, D. (1979). On the use of aqueous space markers to determine the mechanism of interaction between phospholipid vesicles (liposomes) and cells. Biochim. Biophys. Acta, 551, 295.PubMedGoogle Scholar
  36. 36).
    Papahadjopoulos, D. and Vail, W.J. (1978). Incorporation of macromolecules within large unilamellar vesicles (LUV). Ann. N.Y. Acad. Sci., 308, 252.Google Scholar
  37. 37).
    Lonborg-Holm, K. and Phillipson, L. (1974). Early interactions between animal viruses and cells. Monographs in Virol., 9, 1.Google Scholar
  38. 38).
    Dimitriadis, G.J. (1978). Translation of rabbit globin mRNA introduced by liposomes into mouse lymphocytes. Nature, 274, 923.PubMedCrossRefGoogle Scholar
  39. 39).
    Ostro, M., Giacomoni, D., Lavelle, D., Paxton, W. and Dray, S. (1978). Evidence for the translation of rabbit globin mRNA after liposome-mediated insertion into a human cell line. Nature, 274, 921.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • D. Papahadjopoulos
    • 1
  • T. Wilson
    • 2
  • R. Taber
    • 3
  1. 1.Cancer Research InstituteUC San Francisco Medical CenterSan FranciscoUSA
  2. 2.Department of Physiology and BiophysicsCMDNJ-Rutgers Medical SchoolPiscatawayUSA
  3. 3.Department of Viral Oncology and Experimental PathologyRoswell Park Memorial InstituteBuffaloUSA

Personalised recommendations