Selective tumor cell targeting by the disaccharide moiety of bleomycin

Zhiqiang Yu, Ryan M. Schmaltz, Trevor C. Bozeman, Rakesh Paul, Michael J. Rishel, Krystal S. Tsosie, Sidney Hecht

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2883-2886
Number of pages4
JournalJournal of the American Chemical Society
Volume135
Issue number8
DOIs
StatePublished - 2013

Fingerprint

Disaccharides
Bleomycin
Tumors
Cells
Neoplasms
Cell Line
Cell culture
Microbubbles
Dyes
MCF-7 Cells
Pancreatic Neoplasms
Imaging techniques
Antineoplastic Agents
Prostate
Pancreas
Prostatic Neoplasms
Breast
Coloring Agents
Cell Culture Techniques
Breast Neoplasms

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Yu, Z., Schmaltz, R. M., Bozeman, T. C., Paul, R., Rishel, M. J., Tsosie, K. S., & Hecht, S. (2013). Selective tumor cell targeting by the disaccharide moiety of bleomycin. Journal of the American Chemical Society, 135(8), 2883-2886. https://doi.org/10.1021/ja311090e

Selective tumor cell targeting by the disaccharide moiety of bleomycin. / Yu, Zhiqiang; Schmaltz, Ryan M.; Bozeman, Trevor C.; Paul, Rakesh; Rishel, Michael J.; Tsosie, Krystal S.; Hecht, Sidney.

In: Journal of the American Chemical Society, Vol. 135, No. 8, 2013, p. 2883-2886.

Research output: Contribution to journalArticle

Yu, Z, Schmaltz, RM, Bozeman, TC, Paul, R, Rishel, MJ, Tsosie, KS & Hecht, S 2013, 'Selective tumor cell targeting by the disaccharide moiety of bleomycin', Journal of the American Chemical Society, vol. 135, no. 8, pp. 2883-2886. https://doi.org/10.1021/ja311090e
Yu, Zhiqiang ; Schmaltz, Ryan M. ; Bozeman, Trevor C. ; Paul, Rakesh ; Rishel, Michael J. ; Tsosie, Krystal S. ; Hecht, Sidney. / Selective tumor cell targeting by the disaccharide moiety of bleomycin. In: Journal of the American Chemical Society. 2013 ; Vol. 135, No. 8. pp. 2883-2886.
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