Glioma targeting and blood-brain barrier penetration by dual-targeting doxorubincin liposomes

被引:174
|
作者
Gao, Jian-Qing [1 ]
Lv, Qing [1 ,2 ]
Li, Li-Ming [1 ]
Tang, Xin-Jiang [1 ]
Li, Fan-Zhu [2 ]
Hu, Yu-Lan [1 ]
Han, Min [1 ]
机构
[1] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmaceut, Hangzhou 310003, Zhejiang, Peoples R China
[2] Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China
基金
高等学校博士学科点专项科研基金; 中国国家自然科学基金;
关键词
Dual-targeting; Liposome; Folate; Transferrin; Blood-brain barrier; Glioma; VECTOR-MEDIATED STRATEGY; DRUG-DELIVERY SYSTEMS; IN-VITRO; FOLATE RECEPTOR; P-GLYCOPROTEIN; ENERGY DEPLETION; TRANSFERRIN; TRANSPORT; THERAPY; CELLS;
D O I
10.1016/j.biomaterials.2013.03.097
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Effective chemotherapy for glioblastoma requires a carrier that can penetrate the blood brain barrier (BBB) and subsequently target the glioma cells. Dual-targeting doxorubincin (Dox) liposomes were produced by conjugating liposomes with both folate (F) and transferrin (Tf), which were proven effective in penetrating the BBB and targeting tumors, respectively. The liposome was characterized by particle size, Dox entrapment efficiency, and in vitro release profile. Drug accumulation in cells, P-glycoprotein (P-gp) expression, and drug transport across the BBB in the dual-targeting liposome group were examined by using bEnd3 BBB models. In vivo studies demonstrated that the dual-targeting Dox liposomes could transport across the BBB and mainly distribute in the brain glioma. The anti-tumor effect of the dual-targeting liposome was also demonstrated by the increased survival time, decreased tumor volume, and results of both hematoxylin eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis. The dual-targeting Dox liposome could improve the therapeutic efficacy of brain glioma and were less toxic than the Dox solution, showing a dual-targeting effect. These results indicate that this dual-targeting liposome can be used as a potential carrier for glioma chemotherapy. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5628 / 5639
页数:12
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