title: Polymeric topology and composition constrained polyether-polyester micelles for directional antitumor drug delivery.
abstract: Amphiphilic linear and dumbbell-shaped poly(ethylene glycol)-poly(lactide-co-glycolide) (PEG-PLGA) copolymers were simply synthesized by the ring-opening polymerization of lactide and glycolide using PEG or tetrahydroxyl-functionalized PEG as the macroinitiator and stannous octoate as the catalyst. The copolymers spontaneously self-assembled into spherical micelles in phosphate-buffered saline at pH 7.4. The self-assembly behavior was dependent on both the polymeric topology and composition. Doxorubicin (DOX), an anthracycline antitumor drug, was loaded into micelles through nanoprecipitation. The in vitro release behavior could be adjusted by regulating the topology or composition of the copolymer, or the pH of the release medium. The effective intracellular DOX release from DOX-loaded micelles was confirmed by confocal laser scanning microscopy and flow cytometry in vitro. DOX-loaded micelles displayed great cellular proliferation inhibition efficacies after incubation for 24, 48 or 72 h. The hemolysis ratio of DOX was significantly reduced by the presence of copolymer. These properties indicated that the micelles derived from linear or dumbbell-shaped copolymers were promising candidates as smart antitumor drug carriers for malignancy therapy.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.forename: Hai
authors.initials: H
authors.lastname: Sun
authors.forename: Jianxun
authors.initials: J
authors.lastname: Ding
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiguo
authors.initials: W
authors.lastname: Xu
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhuang
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002850:Chromatography, Gel; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects; D004986:Ether / Q000138:chemical synthesis / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011098:Polyglactin 910 / Q000138:chemical synthesis / Q000737:chemistry*; D011817:Rabbits; D012996:Solutions; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011091:Polyesters; D012996:Solutions; D013501:Surface-Active Agents; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D004986:Ether; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Composition; Controlled release; Malignancy therapy; Micelle; Topology