Novel Reduction-responsive Branched Polylysine <italic style="font-style: italic">via</italic> Ring-opening Reactions for Gene Delivery

Yi-ming Chen; Yu Qi; Wen-ting Hu; Di Zheng; Bing-ran Yu; Fu-jian Xu

doi:10.11777/j.issn1000-3304.2019.18260

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

Research Article | 更新时间：2021-01-26

- Novel Reduction-responsive Branched Polylysine via Ring-opening Reactions for Gene Delivery
- Acta Polymerica Sinica Vol. 50, Issue 6, Pages: 602-612(2019)
- 作者机构：
  
  生物医用材料北京实验室北京化工大学　北京 100029
- 作者简介：
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2019.18260
  CLC：
- Published：2019-6，
  
  Published Online：31 January 2019，
  
  Received：29 November 2018，
  
  Revised：22 December 2018，
扫描看全文
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 50(6):602-612(2019)
DOI：

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 50(6):602-612(2019) DOI： 10.11777/j.issn1000-3304.2019.18260.

摘要

通过“一锅法”开环反应构建了一种含有双硫键的还原响应型可降解支化聚赖氨酸基因载体(SS-HP). 同时通过相似的方法合成了不含双硫键的支化聚赖氨酸基因载体(CC-HP)作为对照. 聚阳离子/pDNA复合物的水合粒径和电位通过动态光散射仪测定，其在还原性环境中的降解情况通过凝胶阻滞电泳、原子力显微镜测试评价. SS-HP和CC-HP的体外转染能力及细胞毒性通过荧光素酶报告基因和MTT法在脑胶质瘤C6和肝癌HepG2细胞中测定. 癌细胞中过量表达的谷胱甘肽能够使SS-HP在细胞内降解，加速pDNA的释放，使该载体有良好的基因转染能力. 同时，载体的可降解性以及由开环反应给载体引入的大量羟基，使载体有较低的细胞毒性. KillerRed蛋白是一种在可见光照射下能产生单线态氧的红色荧光蛋白. 使用SS-HP携载pKillerRed (pKR)质粒进行体外光动力抗癌评价. SS-HP/pKR转染C6细胞后能成功表达出KillerRed蛋白，光照后可以促进肿瘤细胞的凋亡.

Abstract

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.

关键词

还原响应生物可降解支化聚合物基因载体

Keywords

Reduction-responsiveBiodegradableBranched polymerGene delivery

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Jiangsu Key Laboratory of Material surface technology, School of Materials Science and Engineering, Jiangsu Collaborative Innovation Center of Photovolatic Science and Engineering, Changzhou University

Department of Material Science and Engineering, Beijing Institute of Petrochemical Thechnology Beijing

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

DOI：10.11777/j.issn1000-3304.2019.18260

摘要

Abstract

关键词

Keywords

references