In a recent study, the well-documented
tumor targeting properties of the
antitumor agent bleomycin (BLM) were studied in cell culture using
microbubbles that had been derivatized with multiple copies of BLM. It was shown that BLM selectively targeted MCF-7 human
breast carcinoma cells but not the "normal" breast cell line MCF-10A. Furthermore, it was found that the BLM analogue
deglycobleomycin, which lacks the
disaccharide moiety of BLM, did not target either cell line, indicating that the BLM
disaccharide moiety is necessary for
tumor selectivity. Not resolved in the earlier study were the issues of whether the BLM
disaccharide moiety alone is sufficient for
tumor cell targeting and the possible cellular uptake of the
disaccharide. In the present study, we conjugated BLM, deglycoBLM, and BLM
disaccharide to the cyanine
dye Cy5**. It was found that the BLM and BLM
disaccharide conjugates, but not the deglycoBLM conjugate, bound selectively to MCF-7 cells and were internalized. The same was also true for the
prostate cancer cell line DU-145 (but not for normal PZ-HPV-7 prostate cells) and for the
pancreatic cancer cell line BxPC-3 (but not for normal SVR A221a pancreas cells). The targeting efficiency of the
disaccharide was only slightly less than that of BLM in MCF-7 and DU-145 cells and comparable to that of BLM in BxPC-3 cells. These results establish that the BLM
disaccharide is both necessary and sufficient for
tumor cell targeting, a finding with obvious implications for the design of novel
tumor imaging and therapeutic agents.