pH and near-infrared light dual-stimuli responsive drug delivery using DNA-conjugated gold nanorods for effective treatment of multidrug resistant cancer cells

摘要

A thiolated pH-responsive DNA conjugated gold nanorod (GNR) was developed as a multifunctional nanocarrier for targeted, pH-and near infrared (NIR) radiation dual-stimuli triggered drug delivery. It was further passivated by a thiolated poly(ethylene glycol)-biotin to improve its cancer targeting ability by specific binding to cancer cell over-expressed biotin receptors. Doxorubicin (DOX), a widely used clinical anticancer drug, was conveniently loaded into nanocarrier by intercalating inside the double-stranded pH-responsive DNAs on the GNR surface to complete the construction of the multifunctional nanomedicine. The nanomedicine can rapidly and effectively release its DOX payload triggered by an acidic pH environment (pH ~ 5) and/or applying an 808 nm NIR laser radiation. Compared to free DOX, the biotin-modified nanomedicine displayed greatly increased cell uptake and significantly reduced drug efflux by model multidrug resistant (MDR) breast cancer cell lines (MCF-7/ADR). The application of NIR radiation further increased the DOX release and facilitated its nuclear accumulation. As a result, this new DNA-GNR based multifunctional nanomedicine exerted greatly increased potency (~ 67 fold) against the MDR cancer cells over free DOX.