Lipophilic Prodrug of Methotrexate in the Membrane of Liposomes Promotes Their Uptake by Human Blood Phagocytes.

摘要: Previously, we showed that incorporation of methotrexate (MTX) in the form a lipophilic prodrug (MTXDG) 100-nm lipid bilayer liposomes egg phosphatidylcholine can allow one to reduce toxicity and improve antitumor efficiency MTX mouse model T-cell leukemic lymphoma. However, our hemocompatibility tests vitro, caused complement (C) activation, obviously due binding on liposome surface fragmentation C3 factor. In this work, studied interactions carrying stabilizing molecules phosphatidylinositol (PI), ganglioside GM1, or conjugate N-carboxymethylated oligoglycine (CMG) with subpopulations human blood leukocytes. Liposomes labeled BODIPY-phosphatidylcholine were incubated whole (30 min 1 h, 37°C), cells lysed hypotonic buffer, fluorescence bound but not internalized by leukocytes was quenched crystal violet. Cell suspensions analyzed flow cytometry. Incorporation MTXDG dramatically enhanced phagocytosis any composition monocytes. Neutrophils consumed much less liposomes. Lymphocytes did accumulate The introduction PI into practically affect specific consumption monocytes, while CMG likely increase rate regardless presence MTXDG. GM1 presumably shielded from monocyte populations increased uptake another population, probably expressing C3b-binding receptors (C3b detected after incubation plasma). shown have different effects TNF-α production activated leukocytes, depending structure molecule.