TY - JOUR
T1 - Targeting the cubilin receptor through the vitamin B12 uptake pathway
T2 - Cytotoxicity and mechanistic insight through fluorescent Re(I) delivery
AU - Viola-Villegas, Nerissa
AU - Rabideau, Amy E.
AU - Bartholoma, Mark
AU - Zubieta, Jon
AU - Doyle, Robert P.
PY - 2009/8/27
Y1 - 2009/8/27
N2 - The intrinsic factor (IF) vitamin B12 ileum anchored receptor, cubilin, mediates endocytotic uptake of the IF complex of vitamin B12 to the blood serum. This receptor was targeted for the selective delivery and accumulation of a new bioprobe, a B12 conjugate of rhenium 2, in the cubilin expressing placental choriocarcinoma BeWo cell line. Competitive uptake and cytotoxicity assays of 2 were investigated and interactions with nuclear DNA explored. In addition, the mechanism of internalization of 2 was confirmed to proceed in an IF-cubilin mediated fashion via siRNA transfection experiments. These studies show the great potential of cubilin as a new target for the delivery of B12 based conjugates for cancer diagnostics and/or treatment.
AB - The intrinsic factor (IF) vitamin B12 ileum anchored receptor, cubilin, mediates endocytotic uptake of the IF complex of vitamin B12 to the blood serum. This receptor was targeted for the selective delivery and accumulation of a new bioprobe, a B12 conjugate of rhenium 2, in the cubilin expressing placental choriocarcinoma BeWo cell line. Competitive uptake and cytotoxicity assays of 2 were investigated and interactions with nuclear DNA explored. In addition, the mechanism of internalization of 2 was confirmed to proceed in an IF-cubilin mediated fashion via siRNA transfection experiments. These studies show the great potential of cubilin as a new target for the delivery of B12 based conjugates for cancer diagnostics and/or treatment.
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U2 - 10.1021/jm900777v
DO - 10.1021/jm900777v
M3 - Article
C2 - 19627091
AN - SCOPUS:69049116221
SN - 0022-2623
VL - 52
SP - 5253
EP - 5261
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 16
ER -