物理化学学报 >> 2014, Vol. 30 >> Issue (2): 345-350.doi: 10.3866/PKU.WHXB201311282

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基于低分子量聚乙烯亚胺和油酸的负电性基因载体

杨阳1, 郭霞2   

  1. 1 四川大学华西医院生物治疗国家重点实验室, 成都610041;
    2 扬州大学化学化工学院, 江苏扬州225002
  • 收稿日期:2013-09-16 修回日期:2013-11-28 发布日期:2014-01-23
  • 通讯作者: 郭霞 E-mail:guoxia@yzu.edu.cn
  • 基金资助:

    国家自然科学基金(21073155,21373179)和美国NIH(CA129835,CA149363,CA151652,CA129421)资助项目

Negatively Charged Lipopolyplex for Gene Delivery Based on Low-Molecular-Weight Polyethylenimine and Oleic Acid

YANG Yang1, GUO Xia2   

  1. 1 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
    2 School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, Jiangsu Province, P. R. China
  • Received:2013-09-16 Revised:2013-11-28 Published:2014-01-23
  • Contact: GUO Xia E-mail:guoxia@yzu.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (21073155, 21373179) and NIH grants, USA (CA129835, CA149363, CA151652, CA129421).

摘要:

构建负电性的基因载体、发展基于低分子量聚乙烯亚胺(PEI)的基因载体对基因传递研究具有重要意义. 本文基于低分子量聚乙烯亚胺(2 kDa)和油酸构建了负电性的基因载体. 它通过混合聚乙烯亚胺(2 kDa)、dsDNA和油酸胶束而自发形成. 该基因载体在血清中很稳定,细胞毒性非常低,可包封80%以上DNA. 通过1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[甲氧基(聚乙二醇2000)]铵盐(DSPE-PEG)对其表面进行修饰,发现多达90%的基因可被细胞摄取.

关键词: 聚乙烯亚胺, 油酸, 基因传递

Abstract:

The development of synthetic vectors based on low-molecular-weight polyethylenimine (PEI) and the construction of negatively charged vectors with high nucleic acid encapsulation are two of the current research trends in gene delivery. In the present study, we developed a stable and negatively charged lipopolyplex based on oleic acid and a low-molecular-weight PEI (2 kDa); it was formed by simultaneously mixing oleic acid micelles and a polyplex produced from PEI (2 kDa) and oligo dsDNA. This lipopolyplex is stable in serum, and because of the low molecular weight of the PEI, the lipopolyplex exhibits very low toxicity. The encapsulation efficiencies of nucleic acids by traditional anionic vectors are low, but very high (more than 80%) by this lipopolyplex. Suitable surface modification with 1,2-distearoryl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethyleneglycol-2000) ammonium salt enabled the lipopolyplex to bind to cells, and a high cellular uptake efficiency (ca 90%) was observed in vitro.

Key words: Polyethylenimine, Oleic acid, Gene delivery

MSC2000: 

  • O648