The carbamoylmannose moiety of bleomycin mediates selective tumor cell targeting

Recently, we reported that both bleomycin (BLM) and its disaccharide, conjugated to the cyanine dye Cy5, bound selectively to cancer cells. Thus, the disaccharide moiety alone recapitulates the tumor cell targeting properties of BLM. Here, we demonstrate that the conjugate of the BLM carbamoylmannose moiety with Cy5 showed tumor cell selective binding and also enhanced cellular uptake in most cancer cell lines. The carbamoyl functionality was required for tumor cell targeting. A dye conjugate prepared from a trivalent cluster of carbamoylmannose exhibited levels of tumor cell binding and internalization significantly greater than those of the simple carbamoylmannose-dye conjugate, consistent with a possible multivalent receptor.