Synthesis of a Novel Polymeric Material Folate-Poly(2-ethyl-2-oxazoline)-Distearoyl Phosphatidyl Ethanolamine Tri-Block Polymer for Dual Receptor and pH-Sensitive Targeting Liposome
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概要
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The in vivo distribution of antitumor drugs is usually lack of selectivity, and thus, leading to a low efficacy of chemotherapy on cancers and high toxicity to normal cells. Receptor-mediated targeting liposome with pH-sensitivity as a dual drug delivery system is one of the efficient approaches to overcome the disadvantages. The study was to synthesize a novel smart polymeric material (folate-poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine, F-PEOz-DSPE), which can combine with the folate-receptor (FR) over-expressed on cancer cells and respond to pH changes in endosome–lysosome system in cancer cells to rapidly release drug simultaneously. The F-PEOz-DSPE was synthesized by the method of asymmetric synthesis of organic polymer and characterized by IR, 1H-NMR, electrospray ionization (ESI)-MS and gel permeation chromatography (GPC). To investigate the properties of targeting and pH-sensitivity of F-PEOz-DSPE, blank liposomes, blank fluorescently labeled liposomes and doxorubicin (DOX)-loaded liposomes containing F-PEOz-DSPE or PEOz-DSPE or DSPE were prepared. The cytotoxicity, cellular uptake and drug cumulative release in vitro were investigated. Blank liposomes modified with PEOz block had little cytotoxicity in vitro. The liposomes containing F-PEOz-DSPE showed a higher affinity to human ovarian cancer cell SKOV3, a FR+ cancer cells, than those with PEOz-DSPE. A higher drug cumulative release from DOX-loaded liposomes containing F-PEOz-DSPE or PEOz-DSPE in vitro was found in phosphate buffered saline at pH 5.0 medium than at pH 7.4. These results indicate that F-PEOz-DSPE exhibits selective targeting, pH-sensitivity and little cytotoxicity, and may be a promising polymeric material for dual receptor and pH-sensitive targeting liposome.
著者
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Zhao Chen
State Key Laboratories For Agrobiotechnology Department Of Biochemistry And Molecular Biology Colleg
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Li Mei
Institute Of Chemical Industry Of Forest Products Chinese Academy Of Forestry
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Wang Yang
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, P. O. Box 603, Beijing 100080, People's Republic of China
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Ma Jie
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences
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Zhao Chen
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences
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Xia GuiMin
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College
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An ZhiJiao
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College
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Li ZiChen
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University
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- Synthesis of a Novel Polymeric Material Folate-Poly(2-ethyl-2-oxazoline)-Distearoyl Phosphatidyl Ethanolamine Tri-Block Polymer for Dual Receptor and pH-Sensitive Targeting Liposome