Co-delivery of pEGFP-hTRAIL and paclitaxel to brain glioma mediated by an angiopep-conjugated liposome

Abstract In this study, we report an angiopep-2 modified cationic liposome (ANG-CLP) for the efficient co-delivery of a therapeutic gene encoding the human tumour necrosis factor-related apoptosis-inducing ligand (pEGFP-hTRAIL) and paclitaxel (PTX) to glioma. The dual targeting co-delivery system (A...

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Bibliographic Details
Published in:Biomaterials 2012-01, Vol.33 (3), p.916-924
Main Authors: Sun, Xiyang, Pang, Zhiqing, Ye, Hongxing, Qiu, Bo, Guo, Liangran, Li, Jingwei, Ren, Jinfeng, Qian, Yong, Zhang, Qizhi, Chen, Jun, Jiang, Xinguo
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Brain glioma
Brain Neoplasms - drug therapy
Brain Neoplasms - metabolism
Cell Line, Tumor
Co-delivery
Dentistry
Dual targeting
Glioma - drug therapy
Glioma - metabolism
Humans
Liposomes - chemistry
Mice
Mice, Inbred BALB C
Microscopy, Atomic Force
Paclitaxel
Paclitaxel - administration & dosage
Paclitaxel - therapeutic use
pEGFP-hTRAIL
Peptides - chemistry
TNF-Related Apoptosis-Inducing Ligand - chemistry
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Summary:Abstract In this study, we report an angiopep-2 modified cationic liposome (ANG-CLP) for the efficient co-delivery of a therapeutic gene encoding the human tumour necrosis factor-related apoptosis-inducing ligand (pEGFP-hTRAIL) and paclitaxel (PTX) to glioma. The dual targeting co-delivery system (ANG-CLP/PTX/pEGFP-hTRAIL) improved uptake and gene expression not only in U87 MG cells and BCECs, but also in the glioma bed and infiltrating margin of intracranial U87 MG glioma-bearing models. The system selectively induces apoptosis in U87 MG cells while reducing toxicity to BCECs. The results of the pharmacodynamics studies showed that the apoptosis of glioma cells in in vitro BBB models and in U87 MG glioma-bearing mice induced by ANG-CLP/PTX/pEGFP-hTRAIL was more apparent and widespread than that induced by single medication systems and unmodified co-delivery system. More importantly, the median survival time of brain tumour-bearing mice treated with ANG-CLP/PTX/pEGFP-hTRAIL was 69.5 days, significantly longer than that of other groups, even longer than the commercial temozolomide group (47 days). Therefore, the dual targeting co-delivery system is a promising drug delivery strategy against glioma.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2011.10.035