期刊
BIOMATERIALS
卷 34, 期 33, 页码 8511-8520出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.07.075
关键词
Magnetic silica PLGA nanoparticles; Transferrin; Doxorubicin; Paclitaxel; Brain glioma
资金
- National Medical Research Council (NMRC, Singapore) [NMRC/EDG/0067/2009]
- National University of Singapore (NUS) [R279-000-257-731]
- Shanghai Municipal Science and Technology Commission Foundation Research Project [12JC1408500]
- Chinese Scholarship Council (CSC, State-Sponsored Graduate Scholarship Program for Building High-Level Universities)
The effective treatment of malignant brain glioma is hindered by the poor transport across the blood-brain barrier (BBB) and the low penetration across the blood-tumor barrier (BTB). In this study, transferrin-conjugated magnetic silica PLGA nanoparticles (MNP-MSN-PLGA-Tf NPs) were formulated to overcome these barriers. These NPs were loaded with doxorubicin (DOX) and paclitaxel (PTX), and their anti-proliferative effect was evaluated in vitro and in vivo. The in vitro cytotoxicity of drug-loaded NPs was evaluated in U-87 cells. The delivery and the subsequent cellular uptake of drug-loaded NPs could be enhanced by the presence of magnetic field and the usage of Tf as targeting ligand, respectively. In particular, cells treated with DOX-PTX-NPs-Tf with magnetic field showed the highest cytotoxicity as compared to those treated with DOX-PTX-NPs-Tf, DOX-PTX-NPs, DOX-PTX-NPs-Tf with free Tf. The in vivo therapeutic efficacy of drug-loaded NPs was evaluated in intracranial U-87 MG-luc2 xenograft of BALB/c nude mice. In particular, the DOX-PTX-NPs-Tf treatment exhibited the strongest anti-glioma activity as compared to the PTX-NPs-Tf, DOX-NPs-Tf or DOX-PTX-NPs treatment. Mice did not show acute toxicity after administrating with blank MNP-MSN-PLGA-Tf NPs. Overall, MNP-MSN-PLGA-Tf NPs are promising carriers for the delivery of dual drugs for effective treatment of brain glioma. (C) 2013 Elsevier Ltd. All rights reserved.
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