International Journal of Nanomedicine 2015-01-01

Reduction-responsive cross-linked stearyl peptide for effective delivery of plasmid DNA.

Chong Yao, Zongguang Tai, Xiaoyu Wang, Jiyong Liu, Quangang Zhu, Xin Wu, Lijuan Zhang, Wei Zhang, Jing Tian, Yuan Gao, Shen Gao

Index: Int. J. Nanomedicine 10 , 3403-16, (2015)

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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.