Details

Autor(en) / Beteiligte

• Li, Xiu-Ying
• Zhao, Yao
• Sun, Meng-Ge
• Shi, Ji-Feng
• Ju, Rui-Jun
• Zhang, Cheng-Xiang
• Li, Xue-Tao
• Zhao, Wei-Yu
• Mu, Li-Min
• Zeng, Fan
• Lou, Jin-Ning
• Lu, Wan-Liang

Titel

Multifunctional liposomes loaded with paclitaxel and artemether for treatment of invasive brain glioma

Ist Teil von

• Biomaterials, 2014-07, Vol.35 (21), p.5591-5604

Ort / Verlag

Netherlands: Elsevier Ltd

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Invasive brain glioma is the most lethal type of cancer and is highly infiltrating. This leads to an extremely poor prognosis and makes complete surgical removal of the tumor virtually impossible. Non-penetration of therapeutic drugs across the blood–brain barrier (BBB), brain cancer stem cells (CSCs), and brain cancer vasculogenic mimicry (VM) results in relapse after surgical and radio therapy. We developed a functional targeting chemotherapy for transporting drugs across the BBB, destroying VM channels, and eliminating CSCs and cancer cells in the brain. The studies were undertaken on brain glioma cells in vitro and in brain glioma-bearing rats. Using paclitaxel as the anticancer drug and artemether as the regulator of apoptosis and inhibitor of VM channels, a kind of functional targeting paclitaxel plus artemether liposomes was developed by modifying two new functional materials: a mannose-vitamin E derivative conjugate (MAN-TPGS1000 ) and a dequalinium-lipid derivative conjugate (DQA-PEG2000 -DSPE). The transport mechanism across the BBB was associated with receptor-mediated endocytosis by MAN-TPGS1000 conjugate via glucose transporters and adsorptive-mediated endocytosis by DQA-PEG2000 -DSPE conjugate via electric charge-based interactions. The efficacy was related to the destruction of VM channels by regulating VM indicators, as well as the induction of apoptosis in brain cancer cells and CSCs by activating apoptotic enzymes and pro-apoptotic proteins and inhibiting anti-apoptotic proteins. These data suggest that the chemotherapy using functional targeting paclitaxel plus artemether liposomes could provide a new strategy for treating invasive brain glioma.