title: Targeted gene delivery to glioblastoma using a C-end rule RGERPPR peptide-functionalised polyethylenimine complex.
abstract: Safe and efficient systems capable of specifically targeting brain tumour cells represent a promising approach for the treatment glioblastoma multiforme. Neuropilin-1 (NRP-1) is over-expressed in U87 glioma cells. In the current study, the tumour specific peptide RGERPPR, which binds specifically to NRP-1, was used as a targeting ligand in a gene delivery strategy for glioblastoma. The RGERPPR peptide was coupled to branched polyethylenimine (PEI, 25kDa) using heterobifunctional Mal-PEG-NHS, resulting in a novel gene delivery polymer. Polymer/plasmid DNA (pDNA) complexes were formed and their sizes and zeta potentials were measured. Compared with the unmodified mPEG-PEI/pDNA complexes, the RGERPPR-PEG-PEI/pDNA complex led to a significant enhancement in intracellular gene uptake and tumour spheroid penetration. Furthermore, the RGERPPR-PEG-PEI/pDNA complex facilitated enhanced transfection efficiency levels, as well as a reduction in cytotoxicity when tested in U87 glioma cells in vitro. Most significantly of all, when complexes formed with pDsRED-N1 were injected into the tail vein of intracranial U87 tumour-bearing nude mice, the RGERPPR-PEG-PEI complexes led to improved levels of red fluorescence protein expression in the brain tissue. Taken together, the results show that RGERPPR-PEG-PEI could be used as a safe and efficient gene delivery vehicle with potential applications in glioblastoma gene delivery.
authors.affiliation: 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.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Lei
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Zuoxu
authors.initials: Z
authors.lastname: Xie
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage; D018014:Gene Transfer Techniques; D005909:Glioblastoma / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D039942:Neuropilin-1 / Q000378:metabolism; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage*; D010957:Plasmids / Q000008:administration & dosage; D011094:Polyethyleneimine / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage; D014162:Transfection / Q000379:methods
chemical_list: D010455:Peptides; D011108:Polymers; C050632:polypeptide C; D039942:Neuropilin-1; D011094:Polyethyleneimine; D004247:DNA
keywords: C-end rule peptide; Gene delivery; Glioma targeting; Neuropilin-1; Polyethylenimine