title: A novel reduction-sensitive modified polyethylenimine oligonucleotide vector.
abstract: A reduction-sensitive cross-linked polyethylenimine derivative PEI-SS-OA was synthesized and evaluated for oligonucleotide delivery. PEI-SS-OA was shown to condense LOR-2501, an oligonucleotide targeting ribonucleotide reductase R1 subunit (RRM1), into positively charged complexes. The reductive degradation of the PEI-SS-OA induced by dithiothreitol was confirmed by a gel retardation assay. In vitro experiments revealed that the reduction-sensitive PEI-SS-OA was less cytotoxic and more effective in oligonucleotide delivery than the control 25kDa PEI. This study demonstrates that a reducibly degradable cationic polymer PEI-SS-OA possesses both higher oligonucleotide delivery efficiency and lower cytotoxicity than PEI (25 kDa), therefore is an attractive candidate for further in vivo evaluation.
authors.affiliation: School of Life Sciences, Jinlin University, Changchun 130012, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Jinlin University, Changchun 130012, China; College of Pharmacy, The Ohio State University, Columbus 43210, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Jinlin University, Changchun 130012, China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Jinlin University, Changchun 130012, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: School of Life Sciences, Jinlin University, Changchun 130012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: School of Life Sciences, Jinlin University, Changchun 130012, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Meng
authors.affiliation: School of Life Sciences, Jinlin University, Changchun 130012, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Jinlin University, Changchun 130012, China. Electronic address: tenglesheng@jlu.edu.cn.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003432:Cross-Linking Reagents / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000737:chemistry; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D009841:Oligonucleotides; D011094:Polyethyleneimine
keywords: Disulfide; Oligonucleotide delivery; Polyethylenimine; Reduction-sensitive