Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment.
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.
School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, PR China.
Yanna
Y
Cui
Qingxing
Q
Xu
Pierce Kah-Hoe
PK
Chow
Deping
D
Wang
Chi-Hwa
CH
Wang
D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
D004317:Doxorubicin; D017239:Paclitaxel
Brain glioma; Doxorubicin; Magnetic silica PLGA nanoparticles; Paclitaxel; Transferrin