title: Reduction-responsive cross-linked stearyl peptide for effective delivery of plasmid DNA.
abstract: Low efficiency and significant toxicity are the main obstacles to successful gene delivery. We have developed a cationic reduction-responsive vector based on a disulfide cross-linked stearylated polyarginine peptide modified with histidine (C-SHR) for DNA delivery. The structure of the C-SHR was characterized, and the in vitro and in vivo transfection efficiency and cytotoxicity of C-SHR/plasmid DNA complexes were examined. Compared with non-cross-linked stearylated polyarginine peptide (SHR), C-SHR increased the intracellular uptake and dissociation behavior of the complexes. In addition, the gene transfection efficiency of C-SHR/plasmid DNA complexes in HEK293 and HeLa cells was improved and was comparable with that of bPEI-25K/plasmid DNA complexes, and the cytotoxicity of C-SHR was significantly less than that of bPEI-25K. Importantly, the in vivo gene transfection efficiency of C-SHR/plasmid DNA complexes was five fold higher than that of SHR/plasmid DNA complexes, suggesting that C-SHR is an efficient non-viral vector for DNA delivery.
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Tai
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China ; Department of Pharmacy, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Quangang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Shanghai Pulmonary Hospital, Shanghai Tongji University, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Shen
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D002412:Cations; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004220:Disulfides / Q000737:chemistry; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000737:chemistry; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010957:Plasmids / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002412:Cations; D003432:Cross-Linking Reagents; D004220:Disulfides; D010455:Peptides; C015462:polyarginine; D004247:DNA
keywords: DNA delivery; histidine; peptide; polyarginine; reduction-responsive; stearyl