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 H₂O_2, 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.