Construction of Functional Targeting Daunorubicin Liposomes Used for Eliminating Brain Glioma and Glioma Stem Cells

被引:20
|
作者
Zhao, Wei-Yu [1 ]
Zhang, Cheng-Xiang [1 ]
Liu, Lei [1 ]
Mu, Li-Min [1 ]
Zeng, Fan [1 ]
Ju, Rui-Jun [1 ]
Xie, Hong-Jun [1 ]
Yan, Yan [1 ]
Zhao, Yao [1 ]
Lu, Wan-Liang [1 ]
机构
[1] Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
基金
中国国家自然科学基金; 北京市自然科学基金;
关键词
Functional Targeting Daunorubicin Liposomes; Brain Glioma Stem Cells; BBB; Apoptotic Signaling Pathways; Efficacy; RESISTANT LUNG-CANCER; BREAST-CANCER; GLUCOSE TRANSPORTERS; IN-VITRO; APOPTOSIS; BARRIER; EXPRESSION; PACLITAXEL; CONJUGATE; DELIVERY;
D O I
10.1166/jbn.2016.2266
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
The highly infiltrative nature of brain glioma makes total surgical removal of cancerous cells virtually impossible. Regular chemotherapy plays an important role in eradicating the residual cancer cells but is ineffective in treating brain glioma due to the hindrance of drug penetration into the tumor site by the blood brain barrier (BBB) and the regeneration of cancer cells by glioma stem cells (GSCs). In this study, functional targeting daunorubicin liposomes were developed by modifying the liposomes with distearoylphosphatidylethanolamine polyethylene glycol-polyethylenimine (DSPE-PEG(2000)-PEI600) and a lipid-glucose derivative (DSPE-PEG(2000)-GLU). The studies were performed in brain glioma and glioma stem cells in vitro and in brain glioma-bearing mice inoculated with the glioma stem cells. The results showed that the functional targeting daunorubicin liposomes were able to significantly transfer across the BBB and exhibited an obvious efficacy in killing glioma and glioma stem cells in mice. The action mechanisms of the functional targeting daunorubicin liposomes were related to their properties: long-duration circulation in the blood system, transport capability across the BBB, concentrated accumulation in the brain glioma site, and increased internalization by malignant cells and their mitochondria. This functional drug formulation showed anticancer efficacy through a direct cytotoxic effect and an apoptosis-inducing effect through the apoptotic signaling pathways in the cytoplasm and mitochondria of the cells. As a chemotherapy strategy for treating brain glioma, functional targeting daunorubicin liposomes have the potential to eliminate brain glioma along with glioma stem cells.
引用
收藏
页码:1404 / 1420
页数:17
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