title: pH and near-infrared light dual-stimuli responsive drug delivery using DNA-conjugated gold nanorods for effective treatment of multidrug resistant cancer cells.
abstract: 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 808nm 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.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
authors.forename: Feihu
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
authors.forename: Jining
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China. Electronic address: srguo@sjtu.edu.cn.
authors.forename: Shengrong
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Electronic address: rongjun.chen@imperial.ac.uk.
authors.forename: Rongjun
authors.initials: R
authors.lastname: Chen
authors.affiliation: School of Chemistry, Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. Electronic address: d.zhou@leeds.ac.uk.
authors.forename: Dejian
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001710:Biotin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D043942:Nanotubes / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D001710:Biotin; D006046:Gold; D004317:Doxorubicin; D004247:DNA
keywords: Cancer; Dual-responsive drug delivery; Gold nanorod; I-motif DNA; Multidrug resistance; Near infrared radiation