pH, redox and photothermal tri-responsive DNA/polyethylenimine conjugated gold nanorods as nanocarriers for specific intracellular co-release of doxorubicin and chemosensitizer pyronaridine to combat multidrug resistant cancer.

Abstract

Pharmacotherapy of multidrug resistant (MDR) cancer remains a challenging task in clinic. Herein, a pH-responsive DNA and disulfide-linked polyethylenimine functionalized gold nanorod was developed for specific co-delivery of chemotherapeutic agent doxorubicin (DOX) and chemosensitizer pyronaridine (PND) to effectively overcome MDR cancer cells. DOX and PND were firstly carried by a multifunctional nanocomplex for reversing MDR cancer. The nanocomplex can responsively and rapidly release its drugs payload under acidic pH environment (pH, ~5), intracellular GSH concentration content (5 mM) and/or 808 nm NIR laser irradiation. Compared to free DOX, the nanocomplex displayed greatly increased cytotoxicity to MDR MCF-7/ADR cancer cells (IC50, 70.68:6.21 μg/mL). The application of NIR radiation further improved the DOX release and enhanced the antitumor effects of the namomedicine (IC50, drops to 2.88 μg/mL). Consequently, this new nanocomplex exerted greatly increased potency against the MDR cancer cells over free DOX (~20 fold).