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Reducible chimeric polypeptide consisting of octa-d-arginine and tetra-l-histidine peptides as an efficient gene delivery vector

Authors Wang X, Tai Z, Tian J, Zhang W, Yao C, Zhang L, Gao Y, Zhu Q, Gao J, Gao S

Received 25 February 2015

Accepted for publication 12 May 2015

Published 22 July 2015 Volume 2015:10(1) Pages 4669—4690

DOI https://doi.org/10.2147/IJN.S83507

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang

Xiaoyu Wang,1,2* Zongguang Tai,1* Jing Tian,1* Wei Zhang,3 Chong Yao,1 Lijuan Zhang,1 Yuan Gao,1 Quangang Zhu,1 Jing Gao,4 Shen Gao1

1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Pharmaceutics, ChengDu Military General Hospital, ChengDu, 3Department of Pharmaceutics, Shanghai Pulmonary Hospital, Tongji University, Shanghai, 4Department of Pharmaceutical Science, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract: Cationic oligopeptide as a nonviral gene delivery vector has aroused much research interest recently, but its further application is limited by its low transfection efficiency. In the present study, we have created a high-efficiency gene vector by using octa-d-arginine and tetra-l-histidine to form a disulfide cross-linked chimeric polypeptide and used this vector to deliver the therapeutic gene tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) to see whether the gene could be transferred and could exert antitumor effects in vitro and in vivo. The result showed that the newly designed vector was able to condense DNA into nanosized polyplexes effectively, thus facilitating its transmembrane transport, promoting its endosomal escape, and finally enabling degradation within the cell. Our study has demonstrated that this chimeric polypeptide is an effective gene carrier in cancer therapy.

Keywords: reducible polypeptide, disulfide bond, octa-d-arginine, tetra-l-histidine, TRAIL

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