响应性阳离子聚合物及聚合物纳米胶束基因载体

王龙海; 张泽; 曾天佑; 夏磊; 聂旋; 陈光; 尤业字

doi:10.11777/j.issn1000-3304.2017.17240

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响应性阳离子聚合物及聚合物纳米胶束基因载体

专论 | 更新时间：2021-01-26

- 响应性阳离子聚合物及聚合物纳米胶束基因载体
- Responsive Cationic Polymer and Cationic Nanomicelle Vectors for Gene Delivery
- 高分子学报 2017年第12期页码：1883-1904
- 作者机构：
  
  中国科学院软物质化学重点实验室中国科学技术大学高分子科学与工程系合肥 230026
- 作者简介：
  
  [ "尤业字, 男, 1971年5月生.中国科学技术大学教授.1996年于合肥工业大学高分子材料科学与工程专业获学士学位, 2003年于中国科学技术大学高分子科学与工程系获博士学位.2003~2004年日本东京工业大学访问学者, 2004~2005年合肥工业大学化工学院副教授, 2005~2008年美国韦恩州立大学药学院访问学者, 2008~2012年中国科学技术大学高分子科学与工程系副教授, 2012年至今, 中国科学技术大学高分子科学与工程系教授、博士生导师; 2011年入选教育部\"新世纪优秀人才\", 2016年获国家杰出青年科学基金.主要研究方向为高分子纳米药物控释构建及肿瘤治疗, 高分子核酸载体的合成和治疗研究" ]
- 基金信息：
  
  国家自然科学基金(51625305);国家自然科学基金(21474097)
- DOI：10.11777/j.issn1000-3304.2017.17240
  中图分类号：
- 纸质出版日期：2017-12-20，
  
  收稿日期：2017-8-27，
  
  修回日期：2017-9-27，
扫描看全文
王龙海, 张泽, 曾天佑, 夏磊, 聂旋, 陈光, 尤业字. 响应性阳离子聚合物及聚合物纳米胶束基因载体[J]. 高分子学报, 2017,(12):1883-1904.

Long-hai Wang, Ze Zhang, Tian-you Zeng, Lei Xia, Xuan Nie, Guang Chen, Ye-zi You. Responsive Cationic Polymer and Cationic Nanomicelle Vectors for Gene Delivery[J]. Acta Polymerica Sinica, 2017,(12):1883-1904.
王龙海, 张泽, 曾天佑, 夏磊, 聂旋, 陈光, 尤业字. 响应性阳离子聚合物及聚合物纳米胶束基因载体[J]. 高分子学报, 2017,(12):1883-1904. DOI： 10.11777/j.issn1000-3304.2017.17240.

Long-hai Wang, Ze Zhang, Tian-you Zeng, Lei Xia, Xuan Nie, Guang Chen, Ye-zi You. Responsive Cationic Polymer and Cationic Nanomicelle Vectors for Gene Delivery[J]. Acta Polymerica Sinica, 2017,(12):1883-1904. DOI： 10.11777/j.issn1000-3304.2017.17240.

摘要

人类多种疾病都与基因的结构或功能改变密切相关，基因治疗已经成为改善人类健康的新兴医学治疗手段，基因治疗的关键在于构筑高效的基因载体.发展生物可降解、具有高转染效率和低毒性的阳离子聚合物基因载体已经成为当今该领域的主要任务.本文主要介绍了对细胞内外的环境差异和外界刺激具有响应性的阳离子聚合物基因载体的合成方法，实现DNA在细胞内的有效释放；构筑不同拓扑结构的聚合物，运用聚合物的拓扑结构来调节DNA与聚合物组装复合体形貌，实现DNA的可控压缩和提高载体的转染效率；通过两亲性阳离子聚合物的自组装形成稳定的阳离子纳米胶束，增加聚合物表面电荷密度，从而有效增强聚合物和DNA结合能力，实现低正负电荷比条件下的DNA压缩和基因的高效表达.

Abstract

Since gene therapy has the potential to alter expression of any gene of interest

itoffers tremendous promise for treating various human diseases including genetic disorders

cancers

viral infections

and cardiovascular diseases. To construct a suitable vector for transferring the therapeutic gene into the target cells of patients is important for achieving successful gene therapy. Cationic polymers have become one of the most promising synthetic vectors for gene transfection in biotechnology over the past two decades because of their advantages of simple preparation and modification. However

they have failed to enter clinical trials due to their low gene transfection efficacy by far. This review highlights some research work on developing Michael addition reaction

thiol-coupling reaction and thiol-exchange reaction for the preparation of stimuli-responsive polymers for helping the release of DNA inside cell and enhancing gene transfection; the fabrication of bioreducible cationic polymers with different topologies (linear structure

branched structure

and hyperbranched structure)

via

Michael addition reaction for tuning the morphology of the formed polymer/DNA polyplex to increase the cell-uptake and gene transfection; the design of newmethods for making the formed polyplex stable in blood system and for long blood circulation time

which can highly increase gene transfection

in vivo

. On the other hand

for most of the cationic polymers

their binding affinity with plasmid DNA is very weak. Therefore

a large excess of cationic polymer is typically required to achieve a complete DNA condensation

which results in high cytotoxicity and instability of the blood system. Herein

we also highlight the methods for the preparation of a novel class of bioreducible cationic nanomicelles with high surface charge using disulfide bonds to connect the cationic shells to the hydrophobic cores

and the bioreducible nanomicelles thus formed with very high binding affinity to DNA

and they can completely condense DNA even at N/P ratio of 1. The resulting nanomicelles/DNA polyplexes exhibit high biocompatibility and perform very effectively as an efficient gene delivery system

so its gene transfection efficiency is close to that of virus. Therefore

the new bioreducible cationic polymer nanomicelles have many potential applications in gene therapy.

关键词

阳离子聚合物响应性纳米胶束基因传递

Keywords

Cationic polymerResponsibilityNanomicellesGene delivery

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