title: Construction of serum resistant micelles based on heparosan for targeted cancer therapy.
abstract: A novel micelle based on heparosan and deoxycholic acid (DOCA) conjugate (HD) as drug carrier was reported here. As the surface was negatively charged, this micelle could resist serum adsorption, showing favorable stability. Moreover, fluorescence observation confirmed that it was able to deliver model hydrophobic drug doxorubicin (DOX) into HeLa cells efficiently. The DOX-loaded micelles showed sustained release behavior at pH 7.4, and accelerated release behavior at pH 5.0 or in the presence of β-glucuronidase, which over-expressed in tumor cells. In vitro cytotoxicity assay demonstrated that the half-maximal inhibitory concentration (IC50) of DOX-loaded micelles against HeLa cells was much lower than that of COS7 cells, showing significant therapeutic distinction between tumor cells and normal cells. Combining with the good biocompatibility and biodegradability of heparosan, this micelle may be promising in clinical application for targeted drug delivery.
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, PR China.
authors.forename: Jing-Xiao
authors.initials: JX
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Burns & Plastic Surgery, Wuxi Third Renmin Hospital, Wuxi 214041, PR China. Electronic address: luguozhong@hotmail.com.
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, PR China. Electronic address: jhchenwhut@126.com.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004187:Disaccharides / Q000008:administration & dosage / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D004187:Disaccharides; D008823:Micelles; C560363:heparosan
keywords: Drug delivery; Heparosan; Micelle; Serum resistance