Efficient Dox Delivery Using DNA-conjugated Gold Nanorods For Treatment Of Multidrug Resistant MCF-7/ADR Cancer Cells

Gold nanorods(GNRs)have shown great promises in cancer imaging,drug/gene delivery and photothermal therapy,due to excellent biocompatibility,low-/non-cytotoxicity,and unique size-and shapeddependent physical/chemical properties.The GNR LSPR absorption band can be tuned to overlap with the NIR transmission window of biological tissues,where NIR radiations which have deep tissue penetration can be effectively absorbed by GNRs and converted into localized heat for effective photothermal therapy.A single-stranded DNA containing 4-stratches of cytosine rich sequences can be reversibly switched between a C-quadruplex(also known as i-motif)and single-stranded structure by cycling the environmental pH between 5 and 7.4 to achieve efficient,pH-triggered release.Moreover,it retained attractive properties such as high cell uptake,low/non-toxicity,high stability in biological buffers and excellent resistance to nuclease degradation.In this study,A thiolated pH-responsive DNA conjugated gold nanorod 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 cellines(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.