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

JOURNAL OF CONTROLLED RELEASE

卷:232

Article

Zhang, Wenjun¹  Wang, Feihu¹  Wang, Yun¹  Wang, Jining¹  Yu, Yanna¹  Guo, Shengrong¹  Chen, Rongjun²  Zhou, Dejian³ 

[1] Shanghai Jiao Tong Univ, Sch Pharm, 800 Dongchuan Rd, Shanghai 200240, Peoples R China

[2] Univ London Imperial Coll Sci Technol & Med, Dept Chem Engn, South Kensington Campus, London SW7 2AZ, England

[3] Univ Leeds, Sch Chem, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England

关键词: I-motif DNA;    Gold nanorod;    Dual-responsive drug delivery;    Near infrared radiation;    Multidrug resistance;    Cancer;   

DOI  :  10.1016/j.jconrel.2016.04.001

来源: Elsevier

【 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 similar to 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 (similar to 67 fold) against the MDR cancer cells over free DOX. (C) 2016 Published by Elsevier B.V.

【 授权许可】

Free