Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment |
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Authors: | Yanna Cui Qingxing Xu Pierce Kah-Hoe Chow Deping Wang Chi-Hwa Wang |
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Institution: | 1. School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, PR China;2. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore;3. Department of General Surgery, Singapore General Hospital, Outram Road, Block 6, Level 7, Singapore 169608, Singapore;4. Office of Clinical Sciences, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore;5. Department of Surgical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore |
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Abstract: | 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. |
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Keywords: | Magnetic silica PLGA nanoparticles Transferrin Doxorubicin Paclitaxel Brain glioma |
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