Abstract
Liposome-encapsulated drugs and fluorescent markers have been proposed as useful tools in studies of cell biology and in chemotherapy1–3. Until recently, this approach has been limited by the lack of means to fix protein ligands, such as antibodies, to liposome surfaces where they can mediate specific interactions with cells. Our newly developed technique4 for the covalent coupling of monoclonal antibodies to small, sonicated liposomes was used to study the specific delivery of methotrexate (MTX) to cellular targets in vitro. Liposomes containing MTX and carboxyfluorescein (CF)5–7 were coupled to monoclonal antibodies against determinants of molecules encoded by the major histocompatibility complex of the murine H–2k haplotype. These were incubated with lipopolysaccharide (LPS)-induced blast cells from CBA (H–2k), or C57BL/6 (B6) (H–2b) spleens. Only spleen cells from the CBA strain showed evidence of drug effect, as indicated by inhibition of radiolabelled deoxyuridine incorporation, demonstrating that the interaction of the liposomes with the cells was specific. With regard to the different determinants, the effect of the liposome-encapsulated MTX was not correlated with the number of liposomes bound to cells. More lipsomes became bound to the H–2Kk molecule than to the H–2 I–Ek molecule, but liposomes bound to the latter were more effective for drug delivery. An endocytic pathway for the liposome-encapsulated drug is suggested by the fact that the effect of the drug in liposomes, but not in free form, was inhibited by the lysosomotropic amine, NH4CI. The techniques described here provide a simple quantitative assay for the ‘endocytic potential’ of any cell-surface determinant for which a ligand, such as an antibody or hormone, is available.
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Leserman, L., Machy, P. & Barbet, J. Cell-specific drug transfer from liposomes bearing monoclonal antibodies. Nature 293, 226–228 (1981). https://doi.org/10.1038/293226a0
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DOI: https://doi.org/10.1038/293226a0
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