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

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 Gao<sup>1

1</sup>Department 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