Targeting of neoglycoprotein-drug conjugates to cultured human embryonal carcinoma cells
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Targeting of neoglycoprotein-drug conjugates to cultured human embryonal carcinoma cells. / Gabius, H J; Bokemeyer, C; Hellmann, T; Schmoll, H J.
In: J CANCER RES CLIN, Vol. 113, No. 2, 1987, p. 126-30.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Targeting of neoglycoprotein-drug conjugates to cultured human embryonal carcinoma cells
AU - Gabius, H J
AU - Bokemeyer, C
AU - Hellmann, T
AU - Schmoll, H J
PY - 1987
Y1 - 1987
N2 - 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.
AB - 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.
KW - Antineoplastic Agents
KW - Cell Line
KW - Cell Survival
KW - Cisplatin
KW - Etoposide
KW - Glycoproteins
KW - Humans
KW - Lectins
KW - Leupeptins
KW - Methotrexate
KW - Pharmaceutical Vehicles
KW - Receptors, Cell Surface
KW - Teratoma
M3 - SCORING: Journal article
C2 - 3031079
VL - 113
SP - 126
EP - 130
JO - J CANCER RES CLIN
JF - J CANCER RES CLIN
SN - 0171-5216
IS - 2
ER -