title: Targeting of neoglycoprotein-drug conjugates to cultured human embryonal carcinoma cells.
abstract: Fluorescent neoglycoproteins were used to screen for the presence and sugar specificities of cell surface lectins in two human embryonal carcinoma cell lines. Efficient labeling correlated with extent of lectin-mediated uptake of neoglycoproteins, as measured by inhibition of DNA synthesis by drug-neoglycoprotein conjugates. These conjugates contain covalently linked carbohydrate moieties on the carriers to render them accessible to the membrane lectins, most effectively galactosides and alpha-glucosides. They furthermore contain chemically linked cytotoxic drugs (etoposide, cis-diamminedichloroplatinum II and methotrexate) which are intracellularly released after lysosomal breakdown of the carrier, as indicated by the effect of leupeptin. Sugars can confer a greater than 10-fold increase in cytotoxic capacity to the nonglycosylated carrier-drug conjugate, nearly reaching the level of toxicity of the freely diffusible drug. Two different neoglycoproteins, reacting with independently targeted membrane lectins, were shown to be useful in a model for combination chemotherapy. These results therefore suggest potential usefulness of custom-made glycosylated carriers in the targeting of therapeutic agents to human embryonal carcinoma cells.
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006023:Glycoproteins / Q000627:therapeutic use*; D006801:Humans; D037102:Lectins; D007976:Leupeptins / Q000494:pharmacology; D008727:Methotrexate / Q000008:administration & dosage; D014677:Pharmaceutical Vehicles; D011956:Receptors, Cell Surface / Q000502:physiology; D013724:Teratoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D006023:Glycoproteins; D037102:Lectins; D007976:Leupeptins; D014677:Pharmaceutical Vehicles; D011956:Receptors, Cell Surface; D005047:Etoposide; C032854:leupeptin; D002945:Cisplatin; D008727:Methotrexate