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具有自清除细胞内产生的 ROS 能力的生物可还原基因传递载体表现出高基因转染。

Bioreducible Gene Delivery Vector Capable of Self-Scavenging the Intracellular-Generated ROS Exhibiting High Gene Transfection.

机构信息

Key Laboratory of Soft Matter Chemistry, Chinese Academy of Science, Department of Polymer Science and Engineering, University of Science and Technology of China , Hefei, Anhui 230026, China.

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, China.

出版信息

ACS Appl Mater Interfaces. 2016 Aug 3;8(30):19238-44. doi: 10.1021/acsami.6b04327. Epub 2016 Jul 22.

DOI:10.1021/acsami.6b04327
PMID:27420138
Abstract

Cationic polymer vectors have received increasing attention for gene delivery in biotechnology over the past 2 decades, but few polymer vectors were used in clinical applications due to their low gene transfection efficacy. One of the major reasons is that the conventional cationic polymers can induce the increasing of intracellular reactive oxygen species (ROS) concentration and oxidative stress, which reduces the gene transfection efficacy. Here, we create a novel class of thioether dendron-branched polymer conjugate and self-assemble this conjugate into bioreducible cationic nanomicelles with disulfide bond connecting the thioether core to the cationic shell. The obtained nanomicelles have a unique ROS self-scavenging ability, thereby dramatically improving gene transfection efficacy.

摘要

在过去的 20 年里,阳离子聚合物载体在生物技术中的基因传递中受到了越来越多的关注,但由于其基因转染效率低,很少有聚合物载体用于临床应用。其中一个主要原因是传统的阳离子聚合物会诱导细胞内活性氧(ROS)浓度和氧化应激的增加,从而降低基因转染效率。在这里,我们构建了一类新型的硫醚树枝状聚合物缀合物,并将该缀合物自组装成具有二硫键连接硫醚核与阳离子壳的生物还原阳离子纳米胶束。所得纳米胶束具有独特的 ROS 自清除能力,从而显著提高了基因转染效率。

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