Targeting the Cubilin Receptor through the Vitamin B12 Uptake Pathway: Cytotoxicity and Mechanistic Insight through Fluorescent Re(I) Delivery
摘要:
The intrinsic factor (IF) vitamin B-12 ileum anchored receptor, cubilin, mediates endocytotic uptake of the IF complex of vitamin B-12 to the blood serum. This receptor was targeted for the selective delivery and accumulation of a new bioprobe, a B-12 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 B-12 based conjugates for cancer diagnostics and/or treatment.