Endocytosis of Cell Surface Molecules and Intracellular Delivery of Materials Encapsulated in Targeted Liposomes

  • Patrick Machy
  • Lee Leserman
Part of the NATO ASI Series book series (NSSA, volume 199)


The principle benefits for pharmacologic purposes of liposomes include the possibility of transporting highly concentrated reagents entrapped in the liposomes’ aqueous spaces or lipid bilayer and their protection against enzymatic degradation. In addition, certain molecules which may have little or no capacity to enter into cells because of their size or charge may be delivered in biologically active form inside cells by virtue of their association with liposomes. This capacity is enhanced when liposomes are targeted to the cell surface by the use of specific ligands such as monoclonal antibodies, which may additionally offer the possibility to concentrate material at the cell surface and to target sub-populations in a heterogeneous mixture of cells (for reviews see Leserman and Machy, 1987; Ostro, 1987).


Acidity Interferon Enzymatic Degradation Half Life Methotrexate 


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  1. Barbet, J., Machy, P. and Leserman, L.D., 1981, Monoclonal antibody covalently coupled to liposomes: specific targeting to cells, J. Supramol. Struct. and Cell Biochem., 16:243.CrossRefGoogle Scholar
  2. Barbet, J., Machy, P., Truneh, A. and Leserman, L.D., 1984, Weak acid- induced release of liposome-encapsulated carboxyfluorescein, Biochim. Biophys.Acta, 772:347.PubMedCrossRefGoogle Scholar
  3. Bayard, B., Leserman, L.D., Bisbal, C. and Lebleu, B., 1985, Antiviral activity in L1210 cells of antibody-targe ted liposcanes containing (2’-5’)oligo(adenylate) analogues, Eur.J.Biochem., 151:319.PubMedCrossRefGoogle Scholar
  4. Goldmacher, V.S., Tinnel, N.L. and Nelson, B.C., 1986, Evidence that pinocytosis in lymphoid cells has a low capacity, J.Cell Biol., 102:1312.PubMedCrossRefGoogle Scholar
  5. Goldstein, J.L., Brown, M.S., Anderson, R.G.W., Russell, D.W. and Schneider, W.J., 1985, Receptor-mediated endocytosis: concepts emerging from the L.D.L. receptor system, Ann.Rev.Cell Biol., 1:1.PubMedCrossRefGoogle Scholar
  6. Haet, C., Ash, J.F. and Singer, S.J., 1980, The antibody-induced clustering and endocytosis of HLA antigens on cultured human fibroblasts. Cell, 21:429.CrossRefGoogle Scholar
  7. Leonetti, J-P., Machy, P., Degols, G., Lebleu, B. and Leserman, L.D., 1989, Antibody-targeted liposomes containing oligodeox5n:ibonucleotide sequences complementary to viral RNA selectively inhibit viral replication. Submitted for publication.Google Scholar
  8. Leserman, L. and Machy, P., 1987, Ligand targeting of liposomes, in “Liposomes: from Biophysics to Therapeutics”, M.J. Ostro, ed.. Marcel Dekker, Inc., New York.Google Scholar
  9. Leserman, L.D., Barbet, J., Kourilsky, F. and Weinstein, J.N., 1980, Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A, Nature, 288:602.PubMedCrossRefGoogle Scholar
  10. Leserman, L.D., Machy, P. and Barbet, J., 1981, Cell specific drug transfer from liposome bearing monoclonal antibodies, Nature, 293:226.PubMedCrossRefGoogle Scholar
  11. Machy, P. and Leserman, L.D., 1983, Small liposomes are better than large liposomes for specific drug delivery in vitro, Biochim.Biophys.Acta, 730:313.PubMedCrossRefGoogle Scholar
  12. Machy, P. and Leserman, L.D., 1984, Elimination or rescue of cells in culture by specifically targeted liposomes containing methotrexate or formyl tetrahydrofolate, EMBO J., 3:1971.PubMedGoogle Scholar
  13. Machy, P. and Leserman, L.D., 1987, “Applications of Liposomes in Cell Biology and Pharmacology”, Editions INSERM, Paris.Google Scholar
  14. Machy, P. and Truneh, A., 1989, Differential half life of major histocompatibility complex encoded class I molecules by T and B lymphoblasts, Mol.Immunol., 26:687.PubMedCrossRefGoogle Scholar
  15. Machy, P., Barbet, J. and Leserman, L.D., 1982a, Differential endocytosis of T and B lymphocyte surface moleciiles evaluated with antibody fluorescent liposomes containing methotrexate, Proc.Natl Acad,Sci, USA, 79:4148.CrossRefGoogle Scholar
  16. Machy, P., Pierres, M., Barbet, J. and Leserman, L.D., 1982b, Drug transfer into lymphoblasts mediated by liposanes bound to distinct sites on H-2 encoded I-A, I-E and K molecules, J.Immunol., 129:2098.PubMedGoogle Scholar
  17. Machy, P., Truneh, A., Gennaro, D. and Hoffstein, S., 1987a, Endocytosis and de novo expression of major histocompatibility complex encoded class I molecules: kinetic and ultrastructural studies, Eur.J.Cell Biol., 45:126.PubMedGoogle Scholar
  18. Machy, P., Truneh, A., Gennaro, D. and Hoffstein, S., 1987b, Major histocompatibility complex class I moleciiLes internalized via coated pits in T lynnphocytes. Nature, 328:724.PubMedCrossRefGoogle Scholar
  19. Machy, P., Lewis, F., McMillan, L. and Jonak, Z., 1988, Gene transfer from targeted liposomes to specific lymphoid cells by electroporation, Proc.Natl.Acad. Sci.USA, 85:8027.PubMedCrossRefGoogle Scholar
  20. Machy, P., Bizozzero, J-P., Reggio, H. and Leserman, L., 1989, Endocytosis, recycling and shedding of major histocompatibility complex-encoded class II molecules by murine B lymphocytes. Submitted for publication.Google Scholar
  21. Milhaud, P.G., Machy, P., Lebleu, B. and Leserman, L., 1990, Antibody targeted liposomes containing poly (rl).poly (rC) exert a specific antiviral and toxic effect on cells primed with interferonsa/ß or y, Biochim.Biophys.Acta, in press.Google Scholar
  22. Noe, C., Hemandez-Borrell, J., Kinsky, S.C., Matsuura, E. and Leserman, L., 1988, Inhibition of cell proliferation with antibody-targeted liposomes containing methotrexate-y-dimyristoylphosphatidylethanolamine, Biochim.Biophys.Acta, 946:253.PubMedCrossRefGoogle Scholar
  23. Olsnes, S., Sandvig, K., Petersen, O.W. and van Deurs, B., 1989, Immuno- toxins — entry into cells and mechanisms of action, Immunol.Today, 10:291.PubMedGoogle Scholar
  24. Ostro, M.J., ed., 1987, “Liposomes: from Biophysics to Therapeutics”, Marcel Dekker, Inc., New York.Google Scholar
  25. Truneh, A. and Machy, P., 1987, Detection of very low receptor numbers on cells by flow cytometry using a sensitive staining method. Cytometry, 8:562.PubMedCrossRefGoogle Scholar
  26. Truneh, A., Machy, P., Barbet, J., Mishal, Z., Lemonnier, F.A. and Leserman, L.D., 1983a, Endocytosis of HLA and H-2 molecules on transformed murine cells measured by fluorescence dequenching of liposome- encapsulated carboxyfluorescein, EMBO J., 2:2285.PubMedGoogle Scholar
  27. Truneh, A., Mishal, Z., Barbet, J., Machy, P. and Leserman, L.D., 1983b, Endocytosis of liposcmes bound to cell surface proteins measured by flow cytometry, Biochem.J., 214:189.PubMedGoogle Scholar
  28. Truneh, A., Mishal, Z. and Leserman, L.D., 1984, A calmodiiLin antagonist increases the rate of endocytosis of liposanes bound to MHC molecules via monoclonal antibodies, Exp.Cell Res., 155:53.CrossRefGoogle Scholar
  29. Truneh, A., Machy, P. and Horan, P.K., 1987, Antibody-bearing liposomes as multicolor immunofluorescence markers for flow cytometry and imaging, J. Immunol.Methods, 100:59.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Patrick Machy
    • 1
  • Lee Leserman
    • 1
  1. 1.Centre d’Immunologie INSERM-CNRS de Marseille-LuminyMarseille Cedex 9France

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