Light-Regulated NO Release as a Novel Strategy To Overcome Doxorubicin Multidrug Resistance

Nitric oxide (NO) release from a suitable NO photodonor ( NOP ) can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin ( DOX ). The strategy may thus increase DOX toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining DOX and NOP showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than DOX . This opens new and underexplored approaches to overcoming the main therapeutic drawbacks of this chemotherapeutic based on light-controlled release of NO.