title: Cisplatin-crosslinked glutathione-sensitive micelles loaded with doxorubicin for combination and targeted therapy of tumors.
abstract: The delivery of combination chemotherapy by nanoscale platforms has been demonstrated to enhance cancer treatment in the clinic. Cisplatin (CDDP)-crosslinked, glutathione-sensitive, tumor-targeting micelles based on carboxymethyl chitosan were designed for synergistic cisplatin-doxorubicin (DOX) combination chemotherapy. In our study, DOX was conjugated to carboxymethyl chitosan through a disulfide bond, which was structurally characterized by1H NMR. The micelles formed by self-assembly were spherical, with the mean diameter of 274nm. The in vitro release studies revealed that the micelles were highly glutathione-sensitive. Cytotoxicity analysis demonstrated that the cisplatin-crosslinked micelles loaded with DOX exhibited enhanced therapeutic efficacy compared with the DOX-loaded nanoparticles, free DOX, and free CDDP. Cellular uptake and intracellular release revealed that the cisplatin-crosslinked micelles loaded with DOX could efficiently deliver and release DOX into the cancer cells. These results clearly indicate that tumor-targeting and glutathione-sensitive micelles provide means for combination drug delivery in cancer treatment.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China.
authors.forename: Xueqiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China.
authors.forename: Lianghong
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China.
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Xiong
authors.affiliation: Biomedical Materials and Engineering Center, Wuhan University of Technology, Wuhan 430070, China. Electronic address: tongttqq@whut.edu.cn.
authors.forename: Tong
authors.initials: T
authors.lastname: Qiu
authors.affiliation: School of Traditional Chinese Medicine, Hubei University for Nationalities, Enshi 445000, China. Electronic address: jade_0422@hotmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers; D005978:Glutathione; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D009369:Neoplasms
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D004317:Doxorubicin; D005978:Glutathione; D002945:Cisplatin
keywords: Carboxymethyl chitosan; Cisplatin; Combination therapy; Doxorubicin; Drug delivery; Micelles