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 language | English |
|---|---|
| Pages (from-to) | 13888-13894 |
| Number of pages | 7 |
| Journal | Journal of the American Chemical Society |
| Volume | 136 |
| Issue number | 39 |
| DOIs | |
| Publication status | Published - 2014 Oct 1 |
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ASJC Scopus subject areas
- Chemistry(all)
- Catalysis
- Biochemistry
- Colloid and Surface Chemistry
Cite this
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 journal › Article
}
TY - JOUR
T1 - An activatable prodrug for the treatment of metastatic tumors
AU - Kim, Eun Joong
AU - Bhuniya, Sankarprasad
AU - Lee, Hyunseung
AU - Kim, Hyun Min
AU - Cheong, Chaejoon
AU - Maiti, Sukhendu
AU - Hong, Kwan Soo
AU - Kim, Jong Seung
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84907483939&partnerID=8YFLogxK
U2 - 10.1021/ja5077684
DO - 10.1021/ja5077684
M3 - Article
C2 - 25238144
AN - SCOPUS:84907483939
VL - 136
SP - 13888
EP - 13894
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 39
ER -