Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment

被引:317
作者
Cui, Yanna [1 ,2 ]
Xu, Qingxing [2 ]
Chow, Pierce Kah-Hoe [3 ,4 ,5 ]
Wang, Deping [1 ]
Wang, Chi-Hwa [2 ]
机构
[1] Tongji Univ, Sch Mat Sci & Engn, Shanghai 201804, Peoples R China
[2] Natl Univ Singapore, Dept Chem & Biomol Engn, Singapore 117576, Singapore
[3] Singapore Gen Hosp, Dept Gen Surg, Singapore 169608, Singapore
[4] Duke NUS Grad Med Sch, Off Clin Sci, Singapore 169857, Singapore
[5] Natl Canc Ctr, Dept Surg Oncol, Singapore 169610, Singapore
基金
英国医学研究理事会;
关键词
Magnetic silica PLGA nanoparticles; Transferrin; Doxorubicin; Paclitaxel; Brain glioma; DRUG; DELIVERY; RECEPTOR; CHEMOTHERAPY; INHIBITION; EFFICACY; SYSTEM; AGENTS;
D O I
10.1016/j.biomaterials.2013.07.075
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:8511 / 8520
页数:10
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