S-Nitrosoglutathione-Releasing Mineralized Nanoparticles Enhance Anticancer Activities of Arsenite by Reversing Drug Resistance
발표자
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초록
내용
Multidrug resistance (MDR) is one of the biggest obstacles for successful therapy of cancers. Thus, overcoming drug resistance is a major challenge for cancer therapy. Of various mechanisms of resistance in tumor cells, we focus on MDR by overexpression of glutathione s-transferases (GSTs). If it is possible to suppress GSTs of MDR cancer cells, drug resistance would be reduced, and therapeutic efficacy of delivered drugs would increase. Herein, we propose a novel strategy to overcome resistance to arsenite by designing mineralized intracellular nanocarriers that simultaneously release a GST inhibitor (S-nitrosoglutathione (GSNO)) and arsenite. In acidic endosomal compartments (~pH 5.0), the mineral phase of the nanoparticles dissolved to release GSNO, which inactivated GSTs, thereby increasing cellular accumulation of apoptotic arsenite. Our mineralized nanoparticles may serve as an efficacious anticancer agent in terms of tumor resistance and selectivity.