title: A reduction-degradable polymer prodrug for cisplatin delivery: Preparation, in vitro and in vivo evaluation.
abstract: We describe the development of novel reduction-sensitive therapeutic micelles consisting of polyethylene glycol-poly-(l-glutamic acid) (PEG-PLG), and conjugate with dithiodipropionic-Pt (IV) (DTDP-Pt). The drug delivery polymeric micelles lie in the covalent conjugation of each cisplatin drug to the PLG chains through a disulfide bond. The resulting micelles show well-controlled cisplatin loading yield, excellent reduction-responsive drug release kinetics, and enhanced in vitro cytotoxicity against cancer cells. The in vivo studies on the subcutaneous human ovarian carcinoma SKOV-3 xenograft model confirmed that PEG-P(LG-DTDP-Pt) micelles showed significant antitumor activity and reduced side effects, compared with free cisplatin. This characteristic drug release profile holds the promise to suppress cancer cell by rapidly releasing a high dose of chemotherapy drugs inside the tumor cells, thereby improving the therapeutic efficacy of the drug payload.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Zhoufeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Huili
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China. Electronic address: chenlijuan125@163.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008823:Micelles; D010084:Oxidation-Reduction; D011108:Polymers / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; D011355:Prodrugs; D002945:Cisplatin
keywords: Cisplatin; Drug delivery; Polymer prodrug; Stimuli-responsive