An Activatable Prodrug for the Treatment of Metastatic Tumors

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 <b>7</b> 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 <b>7</b> was investigated by monitoring fluorescence after addition of H₂O₂ to the cancer cells. Prodrug <b>7</b> activated by H₂O_2, 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 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