[The influence of carbohydrate ligands on the cytotoxicity of liposomes bearing a methotrexate-diglyceride conjugate in human acute leukemia cell cultures].
The efficiency of the chemotherapeutic agent methotrexate (MTX) in tumor cells is limited by the frequent development of the drug resistance of tumor cells. We had previously shown in vitro using human acute leukemia cells with various sensitivity to MTX (T-lymphoblastic CCRF-CEM line and resistant CEM/MTX subline) that MTX incorporation into liposomes as a lipophilic prodrug, diglyceride conjugate (MTX-DG), allows for the overcoming of cell resistance due to the impaired active transmembrane transport. In this work, we have studied the profile of binding with carbohydrates of the cell lines mentioned using carbohydrate fluorescent probes (poly(acryl amide) conjugates). Lipophilic conjugates of tetrasaccharide SiaLe(x), 6'-HSO3LacNAc, and also inactive pentaol for incorporation into liposomes, have been synthesized. The cytotoxicity of MTX-DG liposomes equipped with the SiaLe(x) ligand toward the sensitive CCRF-CEM cell culture was demonstrated to be 3.5 times higher than that of MTX-DG liposomes bearing the control inactive pentaol. The activity of MTX liposomes bearing 6'-HSO3LacNAc toward resistant CEM/MTX was 1.6-fold increased. The use of carbohydrate ligands as molecular addresses for drug-carrying liposomes as a potential method of treating heterogeneous tumor tissue is discussed.
Kuznetsova
N R
NR
Gaenko
G P
GP
Khaĭdukov
S V
SV
Bovin
N V
NV
Vodovozova
E L
EL
D000180:Acrylic Resins / Q000737:chemistry*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004075:Diglycerides / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008727:Methotrexate / Q000008:administration & dosage* / Q000494:pharmacology; D000099166:Polyacrylamides
D000180:Acrylic Resins; D000964:Antimetabolites, Antineoplastic; D004075:Diglycerides; D005456:Fluorescent Dyes; D008024:Ligands; D008055:Lipids; D008081:Liposomes; D008727:Methotrexate; D000099166:Polyacrylamides; C013965:diolein