Hypoxia-responsive fluorescent amonafide prodrugs for biomarker-activated cancer Theranostics

초록

Amonafide, an anthracene derivative, exerts anticancer effects through DNA intercalation and topoisomerase II inhibition, but its clinical use is limited by low efficacy and severe side effects. To address these limitations, we designed biomarker-responsive amonafide-based prodrugs for selective activation in tumor microenvironments enriched with nitroreductase (NTR) or hydrogen sulfide (H2S). Among them, Amo-c-NO2 exhibited the most potent anticancer activity and selective fluorescence activation at 585 nm in response to NTR, enabling real-time tumor imaging, in both live cells and 3D tumor spheroid models. Once activated, Amo-c-NO2 translocates from mitochondria to the nucleus, inducing apoptosis via topoisomerase inhibition and DNA damage. In vivo, it effectively suppressed tumor growth with minimal side effects. These findings establish Amo-c-NO2 as a promising biomarker-activated theranostic agent for precise and effective cancer therapy.

키워드