期刊
JOURNAL OF CONTROLLED RELEASE
卷 141, 期 2, 页码 183-192出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2009.09.020
关键词
Dual-targeting; Daunorubicin liposomes modified with MAN and TF; Blood-brain barrier; Brain glioma-bearing rats; Survival
资金
- National Basic Research Program of China (973 program) [2007CB935801]
- National Science Foundation of China [30772664]
- Education Ministry of China [20070001741]
Chemotherapy for brain glioma has been of limited value due to the inability of transport of drug across the blood-brain barrier (BBB) and poor penetration of drug into the tumor. For overcoming these hurdles, the dual-targeting daunorubicin liposomes were developed by conjugating with p-aminophenyl-alpha-D-mannopyranoside (MAN) and transferrin (TF) for transporting drug across the BBB and then targeting brain glioma. The dual-targeting effects were evaluated on the BBB model in vitro, C6 glioma cells in vitro, avascular C6 glioma tumor spheroids in vitro, and C6 glioma-bearing rats in vivo, respectively. After applying dual-targeting daunorubicin liposomes, the transport ratio across the BBB model was significantly increased up to 24.9%. The most significant uptake by C6 glioma was evidenced by flow cytometry and confocal microscope. The C6 glioma spheroid volume ratio was significantly lowered to 54.7%. The inhibitory rate to C6 glioma cells after crossing the BBB was significantly enhanced up to 64.0%. The median survival time of tumor bearing rats after administering dual-targeting daunorubicin liposomes (22 days) was significantly longer than that after giving free daunorubicin (17 days, P = 0.001) or other controls. In conclusion, the dual-targeting daunorubicin liposomes are able to improve the therapeutic efficacy of brain glioma in vitro and in animals. (C) 2009 Elsevier B.V. All rights reserved.
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