title: 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 (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.
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors: Xiyang
authors: X
authors: Sun
authors: Zhiqing
authors: Z
authors: Pang
authors: Hongxing
authors: H
authors: Ye
authors: Bo
authors: B
authors: Qiu
authors: Liangran
authors: L
authors: Guo
authors: Jingwei
authors: J
authors: Li
authors: Jinfeng
authors: J
authors: Ren
authors: Yong
authors: Y
authors: Qian
authors: Qizhi
authors: Q
authors: Zhang
authors: Jun
authors: J
authors: Chen
authors: Xinguo
authors: X
authors: Jiang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D018625:Microscopy, Atomic Force; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D010455:Peptides / Q000737:chemistry*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry*
chemical_list: C531860:Angiopep-2; D008081:Liposomes; D010455:Peptides; D053221:TNF-Related Apoptosis-Inducing Ligand; D017239:Paclitaxel