An activatable prodrug for the treatment of metastatic tumors

Eun Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Sukhendu Maiti, Kwan Soo Hong, Jong Seung Kim

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential antimetastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2, selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective antitumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anticancer drug, SN-38.

Original languageEnglish
Pages (from-to)13888-13894
Number of pages7
JournalJournal of the American Chemical Society
Volume136
Issue number39
DOIs
Publication statusPublished - 2014 Oct 1

ASJC Scopus subject areas

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

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    Kim, E. J., Bhuniya, S., Lee, H., Kim, H. M., Cheong, C., Maiti, S., Hong, K. S., & Kim, J. S. (2014). An activatable prodrug for the treatment of metastatic tumors. Journal of the American Chemical Society, 136(39), 13888-13894. https://doi.org/10.1021/ja5077684