Citation: Yi-ming Chen, Yu Qi, Wen-ting Hu, Di Zheng, Bing-ran Yu, Fu-jian Xu. Novel Reduction-responsive Branched Polylysine via Ring-opening Reactions for Gene Delivery[J]. Acta Polymerica Sinica, ;2019, 50(6): 602-612. doi: 10.11777/j.issn1000-3304.2019.18260 shu

Novel Reduction-responsive Branched Polylysine via Ring-opening Reactions for Gene Delivery

Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029

Corresponding author: Bing-ran Yu, yubr@mail.buct.edu.cn Fu-jian Xu, xufj@mail.buct.edu.cn
Received Date: 29 November 2018
Revised Date: 22 December 2018
Available Online: 31 January 2019

Gene therapy is widely concerned as an excellent treatment for cancer. One of the most important things in gene therapy is to construct gene delivery systems with good biodegradability, biocompatibility, and gene delivery capability. Biodegradable non-viral gene vectors based on different microenvironments between cancer cells and normal cells have been paid more attention. In this work, the reduction-responsive branched polylysine (SS-HP) with disulfide bonds was synthesized via a one-pot ring-opening reaction. To make a comparison, the branched polylysine without disulfide bonds (CC-HP) was synthesized by the same method. All the SS-HP/pDNA and CC-HP/pDNA complexes with various weight ratios were prepared by mixing polycation-based solution and pDNA solution completely, and stood for 30 min. The particle size and zeta potential of SS-HP/pDNA and CC-HP/pDNA were measured by dynamic light scattering (DLS). The degradability of polyplexes in reductive environment was visualized by agarose gel electrophoresis and atomic force microscopy (AFM). The in vitro transfection efficiencies and cell viability of SS-HP and CC-HP were evaluated in C6 and HepG2 cell lines using luciferase reporter gene, green fluorescence protein gene, and MTT assay. The concentration of reductive glutathione (GSH) is higher in some cancer cells than that in normal cells. SS-HP showed high gene transfection efficiency in vitro due to the breakdown of reduction-responsive disulfide bonds. Moreover, SS-HP exhibited low cytotoxicity due to the good biodegradability of SS-HP and plenty of hydroxy groups induced by ring-opening reactions. KillerRed protein is a red fluorescence protein which could produce reactive oxygen species (ROS) upon the induction of visible light. From in vitro antitumor assays, the plasmid pKillerRed (pKR) delivered by SS-HP was expressed in C6 cells. KillerRed protein expressed in C6 cells could contribute to the cell apoptosis via photodynamic therapy (PDT). This study provides a novel approach for designing the next-generation gene delivery systems.
- Reduction-responsive,
- Biodegradable,
- Branched polymer,
- Gene delivery
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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

Novel Reduction-responsive Branched Polylysine via Ring-opening Reactions for Gene Delivery

南开大学师唯/华北电力大学（保定）刘景维：二维配位聚合物中有序的亲锂冠醚位点用于无枝晶锂沉积

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通讯作者: 陈斌, bchen63@163.com