title: Construction of polymer-paclitaxel conjugate linked via a disulfide bond.
abstract: Covalently linked amphiphilic polymer-paclitaxel (PTX) could self-assemble into micelles to overcome many drawbacks of existing delivery systems of PTX by virtue of tunable compositions, variable sizes, high drug loading content and zero burst release. Moreover, a reduction-responsive system based on glutathione (GSH) can be established by introducing disulfide bonds into the polymeric carriers to improve the selectivity for cancer cells. Herein, we reported a disulfide bond linked polymer-PTX, P(PEGMEA)-co-P(PDPHEMA)-g-PTX with a high PTX loading content of 43.7 wt.%. In vitro cell assay showed that the polymer carrier has almost no cytotoxicity. The half maximal inhibitory concentration (IC50) values of the polymer-PTX conjugate against HEK-293 cells was about 10 times higher than that of HeLa cells after incubation for 72 h. Such a dramatic selectivity for cancer and normal cells provides a promising strategy to improve the therapeutic efficacy and decrease the side effects of PTX in chemotherapy.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Yuchi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Wulian
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China. Electronic address: yangdong@fudan.edu.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D017239:Paclitaxel
keywords: Drug delivery system; PTX; Polymer–drug conjugate; Reduction responsive