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学科主题: 药学
题名:
A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas
作者: 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
发表日期: 2012-05-01
DOI: 10.1016/j.biomaterials.2012.02.004
卷: 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
所属项目编号: 2007CB935800-2007CB935801 ; 20974004
项目资助者: National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China (NSFC)
WOS记录号: WOS:000303273200013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66176
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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