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A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas
Li, Yan1,2; He, Hai1,2; Jia, Xinru1,2; Lu, Wan-Liang3; Lou, Jinning4; Wei, Yen5
关键词Blood-brain barrier (BBB) PAMAM Dual-targeting PH-sensitive Gliomas
刊名BIOMATERIALS
2012-05-01
DOI10.1016/j.biomaterials.2012.02.004
33期:15页:3899-3908
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]DRUG-DELIVERY ; BIOLOGICAL APPLICATIONS ; MULTIDRUG-RESISTANCE ; IN-VITRO ; CANCER ; DOXORUBICIN ; LIPOSOMES ; RECEPTOR ; TUMORS ; NANOPARTICLES
英文摘要

A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (TO conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced. (C) 2012 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000303273200013
引用统计
被引频次:157[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66176
专题北京大学药学院
作者单位1.Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China
2.Peking Univ, Coll Chem & Mol Engn, Minist Educ, Beijing Natl Lab Mol Sci, Beijing 100871, Peoples R China
3.Peking Univ, Coll Chem & Mol Engn, Minist Educ, Key Lab Polymer Chem & Phys, Beijing 100871, Peoples R China
4.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China
5.Minist Hlth, China Japan Friendship Hosp, Inst Clin Med Sci, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Li, Yan,He, Hai,Jia, Xinru,et al. A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas[J]. BIOMATERIALS,2012,33(15):3899-3908.
APA Li, Yan,He, Hai,Jia, Xinru,Lu, Wan-Liang,Lou, Jinning,&Wei, Yen.(2012).A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.BIOMATERIALS,33(15),3899-3908.
MLA Li, Yan,et al."A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas".BIOMATERIALS 33.15(2012):3899-3908.
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