高等学校化学学报 ›› 2020, Vol. 41 ›› Issue (2): 235-242.doi: 10.7503/cjcu20190637

• 庆祝《高等学校化学学报》复刊40周年专栏 • 上一篇    下一篇

聚谷氨酸接枝聚乙二醇@碳酸钙遮蔽体系用于提高聚乙烯亚胺基因转染效率

郭兆培,林琳,陈杰,田华雨(),陈学思   

  1. 中国科学院长春应用化学研究所, 生态环境高分子材料重点实验室, 长春 130022
  • 收稿日期:2019-12-09 出版日期:2020-02-10 发布日期:2020-01-10
  • 通讯作者: 田华雨 E-mail:thy@ciac.ac.cn
  • 基金资助:
    国家自然科学基金(51925305);国家自然科学基金(51873208);国家自然科学基金(51520105004);国家自然科学基金(51973217);国家自然科学基金(51803210);吉林省科技发展项目资助(20180414027GH)

Polyglutamic Acid Grafted Polyethylene Glycol@Calcium Carbonate Based Shielding System for Improving Polyethyleneimine Gene Transfection Efficiency

GUO Zhaopei,LIN Lin,CHEN Jie,TIAN Huayu(),CHEN Xuesi   

  1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022
  • Received:2019-12-09 Online:2020-02-10 Published:2020-01-10
  • Contact: Huayu TIAN E-mail:thy@ciac.ac.cn
  • Supported by:
    ? Supported by the National Natural Science Foundation of China(51925305);Supported by the National Natural Science Foundation of China(51873208);Supported by the National Natural Science Foundation of China(51520105004);Supported by the National Natural Science Foundation of China(51973217);Supported by the National Natural Science Foundation of China(51803210);the Science and Technology Development Project of Jilin Province, China(20180414027GH)

摘要:

设计并合成了聚谷氨酸-聚乙二醇@碳酸钙(PPG@CaCO3)纳米遮蔽体系, 用于遮蔽聚乙烯亚胺(PEI). 一方面, 聚谷氨酸-聚乙二醇(PPG)可以降低PEI引起的细胞毒性, 更有利于体内应用; 另一方面, CaCO3可有效改善PPG导致的转染效率下降, 并在一定程度上提高PEI的细胞转染效率. 对比遮蔽体系PPG@CaCO3和聚谷氨酸-聚乙二醇@磷酸钙[PPG@Ca3(PO4)2]发现, PPG@CaCO3在微酸性环境中释放二氧化碳气体是提高细胞转染效率的关键因素. 小鼠体内循环实验表明, PPG@CaCO3遮蔽体系可以增加载体在血液中的循环时间. 因此, PPG@CaCO3遮蔽体系对于改善阳离子类基因载体的体内应用起到重要作用.

关键词: 聚乙烯亚胺, 基因转染, 遮蔽体系, 聚谷氨酸-聚乙二醇@碳酸钙

Abstract:

Cationic polymers, especially polyethyleneimine(PEI), have received much attention in the field of non-viral vectors, for their better biological safety and high efficiency gene transfection. However, their higher positive charge density will produce greater cytotoxicity, and also, easily forming larger particles with protein, which limits their further usage in vivo. In this work, we designed a shielding system based on polyglutamic acid-polyethylene glycol@calcium carbonate(PPG@CaCO3) for shielding polyethyleneimine(PEI). On one hand, PGA-PEG(PPG) can reduce the cytotoxicity caused by PEI, and is conducive to applied in vivo. On the other hand, CaCO3 effectively offset the decreased transfection efficiency that caused by PPG, and even enhanced cell transfection efficiency of PEI. Compared with the polyglutamic acid-polyethylene glycol @calcium phosphate[PPG@Ca3(PO4)2], CaCO3 releases carbon dioxide gas in acidic environment, which is a key factor to improve cell transfection efficiency. In vivo circulation experiments in mice show that the shielding system based on PPG@CaCO3 can effectively enhance long circulation. Therefore, the shielding system plays an important role in promoting the in vivo application of cationic gene vectors.

Key words: Polyethyleneimine, Gene transfection, Shielding system, Polyglutamic acid grafted polyethylene glycol@CaCO3

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