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

Abstract

Nitric oxide (NO) release from a suitable NO photodonor (<b>NOP</b>) 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 (<b>DOX</b>). The strategy may thus increase <b>DOX</b> toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining <b>DOX</b> and <b>NOP</b> showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than <b>DOX</b>. This opens new and underexplored approaches to overcoming the main therapeutic drawbacks of this chemotherapeutic based on light-controlled release of NO.