title: 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).
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Feihu
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. Electronic address: shenyuanyuan@sjtu.edu.cn.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: School of Pharmacy, Hubei University of Science and Technology, Xianning, China. Electronic address: hst6511@163.com.
authors.forename: Shengtang
authors.initials: S
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. Electronic address: srguo@sjtu.edu.cn.
authors.forename: Shengrong
authors.initials: S
authors.lastname: Guo
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D004247:DNA; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers; D006046:Gold; D006801:Humans; D006863:Hydrogen-Ion Concentration; D043942:Nanotubes; D010084:Oxidation-Reduction; D011094:Polyethyleneimine; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006046:Gold; D004317:Doxorubicin; D011094:Polyethyleneimine; D004247:DNA
keywords: Disulfide-linked polyethylenimine; Gold nanorods; Multidrug resistant cancer; P-gp inhibitor pyronaridine; pH-responsive DNA