Abstract
We have studied a number of permutations on the use of antibody and antigen for targeting liposomes in vitro. Our first strategy was to make liposomes with lipid bearing the dinitrophenyl (DNP) hapten. These liposomes bound specifically to cells in three experimental configurations: (i) with TNP-modified human peripheral blood lymphocytes as targets and sheep IgG anti-TNP as cross-linking agent; (ii) with murine myeloma MOPC 315 cells (which bear an IgA with high affinity for nitrophenyl haptens) as target, using endogeneous surface immunoglobulin on the cells as a point of attachment; (iii) with Fc-receptor bearing cells as targets and rabbit anti-TNP as an opsonizing agent. We monitored the interactions by encapsulating carboxyfluorescein and/or methotrexate in the liposomes, and in some experiments by incorporating 14C-dipalmitoyl phosphatidylcholine or a fluorescent marker in the lipid. In each study large numbers of liposomes could be bound specifically to the target cells, but they were internalized in significant numbers only in (iii) when cells capable of Fc-mediated endocytosis were used. The most striking internalization was found with the mouse macrophage line P388D1. Encapsulated methotrexate had a several-fold greater effect on the metabolism of P388D1 (as assayed by 3H-deoxyuridine uptake) than did an equivalent amount of methotrexate free in solution. This finding indicated that an appropriately chosen drug can escape the phagosomal system to exert its effect in the cytoplasm.
Our second principal effort has been to couple immunoglobulin to liposomal phosphatidylethanolamine covalently, or else through covalently coupled Staphylococcus aureus protein A. Coupling is achieved with the heterobifunctional agent N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). This method of coupling results in minimal aggregation and little leakage of vesicle contents. Liposomes bearing covalently coupled monoclonal antibody bind with high specificity to cells with the corresponding determinants.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Barbet, J., Machy,P., and Leserman, L.D., 1981, Monoclonal antibody covalently coupled to liposomes: Specific targeting to cells, J. Supramolec. Struct. Cell Biochem., in press.
Cabantchik, Z.I., Volsky, D.J., Ginsberg, H., and Loyter, A., Reconstitution of the erythrocyte anion transport system: in vitro and in vivo approaches, Ann. N.Y. Acad. Sci., U.S.A. 341: 444.
Eisen, H.N., Simms, E.S., and Potter, M., 1968, Mouse myeloma proteins with anti-hapten antibody activity. The protein produced by plasma cell tumor MOPC-315, Biochemistry 7: 4126.
Fraley, R., and D. Papahadjopoulos, D., 1981, New generation liposomes: the engineering of an efficient vehicle for intracellular delivery of nucleic acids, T.I.B.S. 9: 467.
Godfrey, W., Doe, B., Wallace, E.F., Bredt, B., and Wofsy, L., 1981, Affinity targeting of membrane vesicles to cell surfaces, Exptl.Cell Research, in press.
Gregoriadis, G., and Neerunjun, D.E., 1975, Homing of liposomes to target cells, Biochem. Biophys. Res. Commun. 65: 537.
Hagins, W.A., and Yoshikami, S., 1978, In: “Vertebrate Photoreceptors,” Fatt, P., and Barlow, H.B., eds., Academic Press, N.Y.
Heath, T.D., Macher, B.A., and Papahadjopoulos, D., 1981, Covalent attachment of immunoglobulins to liposomes via glycosphingolipids, Biochem. Biophys. Acta, 640: 66.
Huang, L., and Kennel, S.J., 1979, Binding of immunoglobulin G to phospholipid vesicles by sonication, Biochemistry, 18: 1702.
Huang, A., Huang., L., and Kennel, S.J., 1980, Monoclonal antibody covalently coupled with fatty acid, J. Biol. Chem., 255: 8015.
Leserman, L.D., Weinstein, J.N., Blumenthal, R., Sharrow, S.O., and Terry, W.D., 1979, Binding of antigen-bearing fluorescent liposomes to the murine myeloma tumor MOPC 315, J. Immunol. 122: 585.
Leserman, L.D., Weinstein, J.N., Moore, J.J., and Terry, W.D., 1980a, Specific interaction of myeloma tumor cells with haptenbearing liposomes containing methotrexate and carboxyfluorescein, Cancer Res., 40: 4768.
Leserman, L.D., Weinstein, J.N., Blumenthal, R., and Terry, W.D., 1980b, Receptor-mediated endocytosis of antibody opsonized liposomes by tumor cells, Proc. Natl. Acad. Sci. U.S.A., 77: 4089.
Leserman, L.D., Barbet, J., Kourilsky, F.M., and Weinstein J.N., 1980c, Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A, Nature, 288: 602.
Leserman, L.D., and Weinstein, J.N., Receptor mediated binding and endocytosis of drug-containing liposomes by tumor cells, in: “Liposomes and Immunobiology,” Tom, B.H., and Six, H.R., eds., Elsevier, Amsterdam (1980).
Magee, W.E., Cronenberger, J.H., and Thor, D.E., 1978, Marked stimulation of lymphocyte-mediated attack on tumor cells by target-directed liposomes containing immune RNA, Cancer Res., 38: 1173.
Martin, F.D., Hubbell, W.L. and Papahadjopoulos, D., 1981, Immunospecific targeting of liposomes to cells: a novel and efficient method for covalent attachment of Fab’ fragments via disulfide bonds, Biochemistry, 20: 4229.
Six, H.R., Uemura, K., and Kinsky, S.C., 1973, Effect of immunoglobulin class and affinity on the initiation of complement-dependent damage to liposomal model membranes sensitized with dinitrophenylated phospholipids, Biochemistry, 12: 4003.
Szoka, F., Magnusson, K.E., Wojcieszyn, J., Hou, Y., Derzko, Z. and Jacobson, K., 1981, Use of lectins and polyethylene glycol for fusion of glycolipid-containing liposomes with eukaryotic cells, Proc. Natl. Acad. Sci. U.S.A., 78: 1685.
Weinstein, J.N., Yoshikami, S., Henkart, P.A., Blumenthal, R., and Hagins, W.A., 1977, Liposome-cell interaction. transfer and intracellular release of a trapped fluorescent marker, Science, 195: 489.
Weinstein, J.N., Blumenthal, R., Sharrow, S.O., and Henkart, P.A., 1978, Antibody-mediated targeting of liposomes; binding to lymphocytes does not ensure incorporation of vesicle contents into the cells. Biochem. Biophys. Acta, 509: 272.
Weissmann, G., Bloomgarden, D., Kaplan, R., Cohen, C., Hoffstein, S., Collins, T., Gotleib, A., and Nagle, D., 1975, A general method for the introduction of enzymes, by means of immunoglobulin-coated liposomes, into lysosomes of deficient cells, Proc. Natl. Acad. Sci. U.S.A., 72: 88.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1982 Plenum Press, New York
About this chapter
Cite this chapter
Weinstein, J.N., Leserman, L.D., Henkart, P.A., Blumenthal, R. (1982). Antibody-Mediated Targeting of Liposomes. In: Gregoriadis, G., Senior, J., Trouet, A. (eds) Targeting of Drugs. NATO Advanced Study Institutes Series, vol 47. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4241-0_11
Download citation
DOI: https://doi.org/10.1007/978-1-4684-4241-0_11
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-4243-4
Online ISBN: 978-1-4684-4241-0
eBook Packages: Springer Book Archive