Molecular Strings Significantly Improved the Gene Transfection Efficiency of Polycations

• DOI: 10.1021/jacs.8b05341
• Publication Date: 2018-08-30T04:09:45Z
• Authors: Huapan Fang; Zhaopei Guo; Lin Lin; Jie Chen; Pingjie Sun; Jiayan Wu; Caina Xu; Huayu Tian; Xuesi Chen
• Keywords: Mice, Inbred BALB C; Cardiolipins; Cell Survival; Gene Transfer Techniques; Molecular Conformation; Membranes, Artificial; DNA; Endosomes; Tosylarginine Methyl Ester; 02 engineering and technology; 01 natural sciences; Endocytosis; 0104 chemical sciences; Cell Line, Tumor; Neoplasms; Animals; Humans; Female; Polylysine; Particle Size; RNA, Small Interfering; 0210 nano-technology

High transfection efficiency and low cytotoxicity are the two key factors to be considered in the design of gene carriers. Herein, a novel and versatile gene carrier (PLL-RT) was prepared by introducing "molecular string" RT (i.e., p-toluylsulfonyl arginine) onto the polylysine backbone. The introduction of RT string contributed to the formation of multiple interactions between the polycationic gene carriers and cell membrane or DNA, as well as adopting α-helix conformation, all of which would be beneficial to enhance the gene transfection. In addition, RT string grafted onto other polycations such as hyperbranced PEI25k and dendrimer PAMAM could also acquire improved transfection efficiency and low cytotoxicity. Moreover, PLL-RT presented significant tumor inhibition effect in vivo. This work provided an effective strategy for constructing novel gene carriers with high transfection and low cytotoxicity.