1 research outputs found
An Activatable Prodrug for the Treatment of Metastatic Tumors
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 (H<sub>2</sub>O<sub>2</sub>), supporting
the hypothesis that a prodrug could be activated by intracellular
H<sub>2</sub>O<sub>2</sub> and lead to a potential antimetastatic
therapy. In this study, prodrug <b>7</b> was designed to be
activated by H<sub>2</sub>O<sub>2</sub>-mediated boronate oxidation,
resulting in activation of the fluorophore for detection and release
of the therapeutic agent, SN-38. Drug release from prodrug <b>7</b> was investigated by monitoring fluorescence after addition of H<sub>2</sub>O<sub>2</sub> to the cancer cells. Prodrug <b>7</b> activated
by H<sub>2</sub>O<sub>2,</sub> selectively inhibited tumor cell growth.
Furthermore, intratracheally administered prodrug <b>7</b> showed
effective antitumor activity in a mouse model of metastatic lung disease.
Thus, this H<sub>2</sub>O<sub>2</sub>-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