한빛사 논문
Eun-Joong Kim†, Sankarprasad Bhuniya†, Hyunseung Lee†, Hyun Min Kim†, Chaejoon Cheong†‡, Sukhendu Maiti *§, Kwan Soo Hong*†‡, and Jong Seung Kim*§
† Division of MR Research, Korea Basic Science Institute, Cheongju 363-883, Korea
‡ Department of Bio-analytical Science, University of Science & Technology, Daejeon 305-350, Korea
§ Department of Chemistry, Korea University, Seoul 136-701, Korea
*Corresponding author : Sukhendu Mait, Kwan Soo Hong, Jong Seung Kim
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 H2O2and 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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