Light-Responsive Biodegradable Nanomedicine Overcomes Multidrug Resistance via NO-Enhanced Chemosensitization

Multidrug resistance (MDR) is responsible for the relatively low effectiveness of chemotherapeutics. Herein, a nitric oxide (NO) gas-enhanced chemosensitization strategy is proposed to overcome MDR by construction of a biodegradable nanomedicine formula based on BNN6/DOX coloaded monomethoxy(polyethylene glycol)–poly(lactic-co-glycolic acid) (mPEG-PLGA). On one hand, the nanomedicine features high biocompatibility due to the high density of PEG and biodegradable PLGA. On the other hand, the nanoformula exhibits excellent stability under physiological conditions but exhibits stimuli-responsive decomposition of BNN6 for NO gas release upon ultraviolet–visible irradiation. More importantly, after NO release is triggered, gas molecules are generated that break the nanoparticle shell and lead to the release of doxorubicin. Furthermore, NO was demonstrated to reverse the MDR of tumor cells and enhance the chemosensitization for doxorubicin therapy.