title: Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles.
abstract: In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery.
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Shi
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: shaobingzhou@swjtu.edu.cn.
authors.forename: Shaobing
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D005492:Folic Acid / Q000737:chemistry; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D004317:Doxorubicin; D005492:Folic Acid; D005978:Glutathione
keywords: Drug delivery; Nanocarrier; Redox-responsive; Star-shaped; Tumor targeting