A self-immolative and DT-diaphorase-activatable prodrug for drug-release tracking and therapy
作者： Bowen Li , Peilian Liu , Donghang Yan , Fang Zeng , Shuizhu Wu
DOI: 10.1039/C7TB00266A
关键词: Drug 、 Chemistry 、 Cytotoxicity 、 Pharmacology 、 Moiety 、 Controlled release 、 Prodrug 、 Internalization 、 Camptothecin 、 Cancer cell
摘要: DT-diaphorase, which catalyzes the reduction of various biological substances like quinones, is overexpressed in some malignant tumors. However, exploiting this attractive property for controlled release an active drug from a prodrug yet to be fully taken advantage of. Herein we report DT-diaphorase-based concomitant drug-release imaging and cancer chemotherapy. This system composed two camptothecin (CPT) moieties as anticancer drug, DT-diaphorase-responsive quinone propionic acid moiety set self-immolative linkers. The presence DT-diaphorase leads CPT molecules restores fluorescence latter, thereby realizing monitoring level well tracking release. Upon internalization by overexpressing cells, can fluorescent exhibit high cytotoxicity (half-maximal inhibitory concentration 0.71 μM) towards cells. features on-demand enzyme-biomarker-triggered self-monitoring release, therapeutic effect biomarker level. new strategy may provide effective approach constructing prodrugs with enhanced loading controllability tracking.
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