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

116 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

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Prodrugs
Tumors
irinotecan
Fluorescence
Pulmonary diseases
Fluorophores
Cell growth
Hydrogen peroxide
Neoplasms
Chemical activation
Cells
Imaging techniques
Oxidation
Oxygen
Monitoring
Optical Imaging
Pharmaceutical Preparations
Hydrogen Peroxide
Lung Diseases
Reactive Oxygen Species

ASJC Scopus subject areas

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

Cite this

Kim, E. J., Bhuniya, S., Lee, H., Kim, H. M., Cheong, C., Maiti, 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

An activatable prodrug for the treatment of metastatic tumors. / Kim, Eun Joong; Bhuniya, Sankarprasad; Lee, Hyunseung; Kim, Hyun Min; Cheong, Chaejoon; Maiti, Sukhendu; Hong, Kwan Soo; Kim, Jong Seung.

In: Journal of the American Chemical Society, Vol. 136, No. 39, 01.10.2014, p. 13888-13894.

Research output: Contribution to journalArticle

Kim, EJ, Bhuniya, S, Lee, H, Kim, HM, Cheong, C, Maiti, S, Hong, KS & Kim, JS 2014, 'An activatable prodrug for the treatment of metastatic tumors', Journal of the American Chemical Society, vol. 136, no. 39, pp. 13888-13894. https://doi.org/10.1021/ja5077684
Kim EJ, Bhuniya S, Lee H, Kim HM, Cheong C, Maiti S et al. An activatable prodrug for the treatment of metastatic tumors. Journal of the American Chemical Society. 2014 Oct 1;136(39):13888-13894. https://doi.org/10.1021/ja5077684
Kim, Eun Joong ; Bhuniya, Sankarprasad ; Lee, Hyunseung ; Kim, Hyun Min ; Cheong, Chaejoon ; Maiti, Sukhendu ; Hong, Kwan Soo ; Kim, Jong Seung. / An activatable prodrug for the treatment of metastatic tumors. In: Journal of the American Chemical Society. 2014 ; Vol. 136, No. 39. pp. 13888-13894.
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