title: Retro-inverso CendR peptide-mediated polyethyleneimine for intracranial glioblastoma-targeting gene therapy.
abstract: The development of nonviral gene delivery vectors offers the potential to provide effective treatment for glioblastoma in the form of gene therapy. Here, we report the use of retro-inverso C-end rule (CendR) peptide D(RPPREGR) as a targeting ligand to prepare a D(RPPREGR)-PEG-PEI gene vector. D(RPPREGR) peptide specifically recognized the neuropilin-1 receptor that was overexpressed on U87 glioma cells, and showed enhanced tumor spheroid penetration ability. Compared with parental RGERPPR, D(RPPREGR) possessed improved biological stability and had a higher affinity for U87 glioma cells; it also showed enhanced penetration of the tumor spheroid. mPEG-PEI/pDNA and D(RPPREGR)-PEG-PEI/pDNA complexes were prepared and MTT assay results revealed that the cytotoxicity of D(RPPREGR)-PEG-PEI complexes was significantly lower than that of PEI complexes, with cell survival rates above 80%. Qualitative and quantitative in vitro transfection results revealed that D(RPPREGR)-PEG-PEI complex transfection efficiencies were 1.9 times higher than those of mPEG-PEI. Fluorescent imaging and frozen sections of brain tissue demonstrated that the D(RPPREGR) modification improved the in vivo transfection efficiency of mPEG-PEI in nude mice bearing U87 gliomas. An antiglioblastoma assay revealed that D(RPPREGR)-PEG-PEI carrying the therapeutic gene pORF-hTRAIL significantly prolonged the survival time of intracranial U87 glioma-bearing mice from 25 to 30 days. Therefore, D(RPPREGR)-PEG-PEI appears to be suitable for use as a safe and efficient gene delivery vehicle with potential applications in glioblastoma gene therapy.
authors: Key Laboratory of Smart Drug Delivery(Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, PR China.
authors: Jing
authors: J
authors: Wang
authors: Yang
authors: Y
authors: Lei
authors: Cao
authors: C
authors: Xie
authors: Weiyue
authors: W
authors: Lu
authors: Ernst
authors: E
authors: Wagner
authors: Zuoxu
authors: Z
authors: Xie
authors: Jie
authors: J
authors: Gao
authors: Xiaoyu
authors: X
authors: Zhang
authors: Zhiqiang
authors: Z
authors: Yan
authors: Min
authors: M
authors: Liu
mesh_terms: D001932:Brain Neoplasms / Q000628:therapy*; D015316:Genetic Therapy; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D010455:Peptides / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*
chemical_list: D010455:Peptides; D011094:Polyethyleneimine