Inhibition of cell proliferation with antibody-targeted liposomes containing methotrexate-γ-dimyristoylphosphatidylethanolamine

Christine Noé, Jordi Hernandez-Borrell, Stephen C. Kinsky, Eiji Matsuura, Lee Leserman

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

We have prepared liposomes containing methotrexate-γ-dimyristoylphosphatidylethanolamine (MTX-DMPE liposomes), to which protein A was covalently coupled, permitting specific association of these liposomes in vitro with murine cells preincubated with relevant protein A-binding monoclonal antibodies. In the absence of antibody the presence of externally-oriented methotrexate (MTX) in MTX-DMPE liposomes did not result in greater binding to cells than liposomes made without MTX-γ-DMPE. Derivation of methotrexate with phospholipid permits enhanced drug-liposome association. These liposomes are more resistant than conventional liposomes to repeated cycles of freezing and thawing. MTX-DMPE liposomes are comparable to antibody-targeted liposomes made with encapsulated water-soluble methotrexate both with respect to specific binding to target cells and drug effect. The inhibitory effects off MTX-liposomes, as well as free MTX, were reversible by either thiamin pyrophosphate (Tpp) or N5-formyltetrahydrofolate (F-THF), while the effects of MTX-DMPE liposomes were reversed only by N5-formyltetrahydrofolate. This suggests that the toxicity of non-targeted MTX-liposomes may be due to leakage of the encapsulated MTX. The absence of an effect of thiamin pyrophosphate on non-targeted MTX-DMPE liposomes indicates that they do not enter into the cell via the normal folate transport system.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalBBA - Biomembranes
Volume946
Issue number2
DOIs
Publication statusPublished - Dec 22 1988
Externally publishedYes

Keywords

  • Drug targeting
  • Methotrexate derivative
  • Monoclonal antibody
  • Phospholipid
  • Receptor mediated endocytosis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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