title: Redox-Sensitive Hydroxyethyl Starch-Doxorubicin Conjugate for Tumor Targeted Drug Delivery.
abstract: Doxorubicin (DOX) is one of the most potent anticancer agents in cancer chemotherapy, but the clinical use of DOX is restricted by its severe side effects caused by nonspecific delivery. To alleviate the side effects and improve the antitumor efficacy of DOX, a novel redox-sensitive hydroxyethyl starch-doxorubicin conjugate, HES-SS-DOX, with diameter of 19.9 ± 0.4 nm was successfully prepared for tumor targeted drug delivery and GSH-mediated intracellular drug release. HES-SS-DOX was relatively stable under extracellular GSH level (∼2 μM) but released DOX quickly under intracellular GSH level (2-10 mM). In vitro cell study confirmed the GSH-mediated cytotoxicity of HES-SS-DOX. HES-SS-DOX exhibited prolonged plasma half-life time and enhanced tumor accumulation in comparison to free DOX. As a consequence, HES-SS-DOX exhibited better antitumor efficacy and reduced toxicity as compared to free DOX in the in vivo antitumor activity study. The redox-sensitive HES-SS-DOX was proved to be a promising prodrug of DOX, with clinical potentials, to achieve tumor targeted drug delivery and timely intracellular drug release for effective and safe cancer chemotherapy.
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors: Hang
authors: H
authors: Hu
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors: Yihui
authors: Y
authors: Li
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors: Qing
authors: Q
authors: Zhou
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors: Yanxiao
authors: Y
authors: Ao
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors: Chan
authors: C
authors: Yu
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors: Ying
authors: Y
authors: Wan
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors: Huibi
authors: H
authors: Xu
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.|Wuhan Institute of Biotechnology , High Tech Road 666, East Lake High Tech Zone, Wuhan 430040, People's Republic of China.
authors: Zifu
authors: Z
authors: Li
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors: Xiangliang
authors: X
authors: Yang
mesh_terms: D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms; D010084:Oxidation-Reduction; D013213:Starch
chemical_list: D004317:Doxorubicin; D013213:Starch
keywords: chemotherapy; conjugate; doxorubicin; hydroxyethyl starch; redox-sensitive; tumor targeted drug delivery