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. 1985 Oct;4(10):2461–2467. doi: 10.1002/j.1460-2075.1985.tb03957.x

LDL-mediated targeting of liposomes to leukemic lymphocytes in vitro.

M Vidal, J Sainte-Marie, J R Philippot, A Bienvenue
PMCID: PMC554530  PMID: 4054094

Abstract

We describe a method for the covalent coupling of low-density lipoproteins (LDL) to the surface of small unilamellar vesicles, and the delivery of the liposome content to leukemic L2C lymphocytes in vitro. We demonstrate the stability of the linkage between LDL and liposomes, the preservation of vesicle integrity and the affinity of the LDL for their specific receptors after the coupling reaction. Hygromycin B, an impermeant inhibitor of protein synthesis, was encapsulated in the targeted liposomes, and delivered into the cytoplasm of leukemic L2C lymphocytes by the LDL pathway, as demonstrated by the lethal effect on cells measured by 51chromium-release assay.

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Selected References

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  1. Allen T. M., McAllister L., Mausolf S., Gyorffy E. Liposome-cell interactions. A study of the interactions of liposomes containing entrapped anti-cancer drugs with the EMT6, S49 and AE1 (transport-deficient) cell lines. Biochim Biophys Acta. 1981 May 6;643(2):346–362. doi: 10.1016/0005-2736(81)90080-8. [DOI] [PubMed] [Google Scholar]
  2. Alonso M. A., Carrasco L. Action of membrane-active compounds on mammalian cells. Permeabilization of human cells by ionophores to inhibitors of translation and transcription. Eur J Biochem. 1980 Aug;109(2):535–540. doi: 10.1111/j.1432-1033.1980.tb04825.x. [DOI] [PubMed] [Google Scholar]
  3. Barbet J., Machy P., Leserman L. D. Monoclonal antibody covalently coupled to liposomes: specific targeting to cells. J Supramol Struct Cell Biochem. 1981;16(3):243–258. doi: 10.1002/jsscb.1981.380160305. [DOI] [PubMed] [Google Scholar]
  4. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  5. Blythman H. E., Casellas P., Gros O., Gros P., Jansen F. K., Paolucci F., Pau B., Vidal H. Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumour cells. Nature. 1981 Mar 12;290(5802):145–146. doi: 10.1038/290145a0. [DOI] [PubMed] [Google Scholar]
  6. CONGDON C. C., LORENZ E. Leukemia in guinea-pigs. Am J Pathol. 1954 Mar-Apr;30(2):337–359. [PMC free article] [PubMed] [Google Scholar]
  7. Cabañas M. J., Vázquez D., Modolell J. Dual interference of hygromycin B with ribosomal translocation and with aminoacyl-tRNA recognition. Eur J Biochem. 1978 Jun 1;87(1):21–27. doi: 10.1111/j.1432-1033.1978.tb12347.x. [DOI] [PubMed] [Google Scholar]
  8. Chuillon Sainte-Marie J., Authier M. H., Cayzac M., Philippot J. R. Plasma lipoproteins of leukemic guinea pigs (L2C) can regulate cholesterol biosynthesis by lymphocytes of normal guinea pigs. A comparative study of plasma lipoproteins of normal and neoplastic animals. Eur J Biochem. 1981 Jun;117(1):219–224. doi: 10.1111/j.1432-1033.1981.tb06325.x. [DOI] [PubMed] [Google Scholar]
  9. Fraley R., Straubinger R. M., Rule G., Springer E. L., Papahadjopoulos D. Liposome-mediated delivery of deoxyribonucleic acid to cells: enhanced efficiency of delivery related to lipid composition and incubation conditions. Biochemistry. 1981 Nov 24;20(24):6978–6987. doi: 10.1021/bi00527a031. [DOI] [PubMed] [Google Scholar]
  10. Goldstein J. L., Anderson R. G., Brown M. S. Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature. 1979 Jun 21;279(5715):679–685. doi: 10.1038/279679a0. [DOI] [PubMed] [Google Scholar]
  11. Goldstein J. L., Basu S. K., Brunschede G. Y., Brown M. S. Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans. Cell. 1976 Jan;7(1):85–95. doi: 10.1016/0092-8674(76)90258-0. [DOI] [PubMed] [Google Scholar]
  12. Goldstein J. L., Brown M. S. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Aug 25;249(16):5153–5162. [PubMed] [Google Scholar]
  13. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Handley D. A., Arbeeny C. M., Witte L. D., Chien S. Colloidal gold--low density lipoprotein conjugates as membrane receptor probes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):368–371. doi: 10.1073/pnas.78.1.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jansons V. K., Panzner E. A. Liposomes as a means to introduce fragment A of diphtheria toxin into cells. Biochim Biophys Acta. 1983 Nov 23;735(3):433–437. doi: 10.1016/0005-2736(83)90159-1. [DOI] [PubMed] [Google Scholar]
  16. Kall M. A., Koren H. S. Human natural killing: evidence for both serum-independent and serum-dependent cytotoxic mechanisms. Cell Immunol. 1979 Sep 15;47(1):57–68. doi: 10.1016/0008-8749(79)90314-9. [DOI] [PubMed] [Google Scholar]
  17. Lavelle D., Paxton W. B., Blaustein D. I., Ostro M. J., Giacomoni D. Improved methods for the delivery of liposome-sequestered RNA into eucaryotic cells. Arch Biochem Biophys. 1982 May;215(2):486–497. doi: 10.1016/0003-9861(82)90107-2. [DOI] [PubMed] [Google Scholar]
  18. Leserman L. D., Machy P., Barbet J. Cell-specific drug transfer from liposomes bearing monoclonal antibodies. Nature. 1981 Sep 17;293(5829):226–228. doi: 10.1038/293226a0. [DOI] [PubMed] [Google Scholar]
  19. Machy P., Barbet J., Leserman L. D. Differential endocytosis of T and B lymphocyte surface molecules evaluated with antibody-bearing fluorescent liposomes containing methotrexate. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4148–4152. doi: 10.1073/pnas.79.13.4148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mahley R. W., Innerarity T. L. Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta. 1983 May 24;737(2):197–222. doi: 10.1016/0304-4157(83)90001-1. [DOI] [PubMed] [Google Scholar]
  21. McIntosh D. P., Heath T. D. Liposome-mediated delivery of ribosome inactivating proteins to cells in vitro. Biochim Biophys Acta. 1982 Sep 9;690(2):224–230. doi: 10.1016/0005-2736(82)90326-1. [DOI] [PubMed] [Google Scholar]
  22. Nicolau C., Sene C. Liposome-mediated DNA transfer in eukaryotic cells. Dependence of the transfer efficiency upon the type of liposomes used and the host cell cycle stage. Biochim Biophys Acta. 1982 Oct 11;721(2):185–190. doi: 10.1016/0167-4889(82)90067-2. [DOI] [PubMed] [Google Scholar]
  23. Potter M. R., Moore M. Natural cytotoxic reactivity of human lymphocyte subpopulations. Immunology. 1979 May;37(1):187–194. [PMC free article] [PubMed] [Google Scholar]
  24. Sainte-Marie J., Vidal M., Philippot J. R., Bienvenüe A. Characterization of low density lipoprotein receptors in freshly isolated leukemic guinea pig lymphocytes (L2C). J Recept Res. 1985;5(2-3):171–192. doi: 10.3109/10799898509041878. [DOI] [PubMed] [Google Scholar]
  25. Steinman R. M., Mellman I. S., Muller W. A., Cohn Z. A. Endocytosis and the recycling of plasma membrane. J Cell Biol. 1983 Jan;96(1):1–27. doi: 10.1083/jcb.96.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thorpe P. E., Ross W. C., Cumber A. J., Hinson C. A., Edwards D. C., Davies A. J. Toxicity of diphtheria toxin for lymphoblastoid cells is increased by conjugation to antilymphocytic globulin. Nature. 1978 Feb 23;271(5647):752–755. doi: 10.1038/271752a0. [DOI] [PubMed] [Google Scholar]
  27. Vidal M., Bienvenue A., Sainte-Marie J., Philippot J. The influence of the internal content of negatively charged liposomes on their interaction with high-density lipoprotein. Eur J Biochem. 1984 Jan 16;138(2):399–405. doi: 10.1111/j.1432-1033.1984.tb07929.x. [DOI] [PubMed] [Google Scholar]

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