Mitochondria-Targeted Photoactivatable Real-Time Monitoring of a Controlled Drug Delivery Platform

The current anticancer therapies
are limited by their lack of controlled
spatiotemporal release at the target site of action. We report a novel
drug delivery platform that provides on-demand, real-time, organelle-specific
drug release and monitoring upon photoactivation. The system is comprised
of a model anticancer drug doxorubicin, an alkyltriphenylphosphonium
moiety to target mitochondria in cancer cells, and a hydroxycinnamate
photoactivatable linker that is covalently attached to the drug and
mitochondria-targeting moieties such that it can be phototriggered
by either UV (one-photon) or NIR (two-photon) light to form a fluorescent
coumarin product and facilitate the release of drug payload. The extent
of drug release is quantified by the fluorescence intensity of the
coumarin formed. Further, the photoactivatable prodrug accumulates
in the mitochondria and shows light-triggered temporally controlled
cell death. In the future, our platform can be tuned for any biological
application of interest, offering immense value in biomedicine.