Real-Time Monitoring of Arsenic Trioxide Release and Delivery by Activatable T₁ Imaging

Abstract

Delivery of arsenic trioxide (ATO), a clinical anticancer drug, has drawn much attention to improve its pharmacokinetics and bioavailability for efficient cancer therapy. Real-time and in situ monitoring of ATO behaviors in vivo is highly desirable for efficient tumor treatment. Herein, we report an ATO-based multifunctional drug delivery system that efficiently delivers ATO to treat tumors and allows real-time monitoring of ATO release by activatable T1 imaging. We loaded water-insoluble manganese arsenite complexes, the ATO prodrug, into hollow silica nanoparticles to form a pH-sensitive multifunctional drug delivery system. Acidic stimuli triggered the simultaneous release of manganese ions and ATO, which dramatically increased the T1 signal (bright signal) and enabled real-time visualization and monitoring of ATO release and delivery. Moreover, this smart multifunctional drug delivery system significantly improved ATO efficacy and strongly inhibited the growth of solid tumors without adverse side effects. This strategy has great potential for real-time monitoring of theranostic drug delivery in cancer diagnosis and therapy.