Acta Chimica Sinica ›› 2013, Vol. 71 ›› Issue (03): 323-333.DOI: 10.6023/A12110974 Previous Articles     Next Articles

Review

pH敏感基因载体的研究现状

沈银a, 胡桂香b, 张华星b, 齐莉莉b, 骆成才b   

  1. a 浙江大学化学系 杭州 310027;
    b 浙江大学宁波理工学院 生物与化学工程分院 宁波 315100
  • 收稿日期:2012-11-28 出版日期:2013-03-14 发布日期:2013-01-31
  • 通讯作者: 骆成才 E-mail:luochengcai@nit.net.cn
  • 基金资助:

    项目受国家自然科学基金(No.21002088)和宁波市自然科学基金(No.2012A610177)资助.

Recent Progress in pH-Sensitive Gene Carriers

Shen Yina, Hu Guixiangb, Zhang Huaxingb, Qi Lilib, Luo Chengcaib   

  1. a Department of Chemistry, Zhejiang University, Hangzhou 310027;
    b School of Biological and Chemical Engineering, Ningbo Institute of Technology, Zhejiang University, Ningbo 315100
  • Received:2012-11-28 Online:2013-03-14 Published:2013-01-31
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21002088) and Ningbo Natural Science Foundation (No. 2012A610177).

Gene therapy shows promise as a potentially revolutionizing strategy for treatment of many genetically-related diseases, such as cancer. However, the lack of safe and effective gene delivery carriers (or vectors) has become a bottleneck in its basic research and clinical application. Generally, gene delivery carriers can be divided into viral and non-viral ones. Although non-viral gene delivery carriers can offer some advantages such as safety and facile fabrication, they don't possess the same high gene delivery efficiency as viral gene delivery carriers do, due to lack of functionality to overcome many intracellular gene-delivery obstacles. Currently, many kinds of "smart" non-viral gene-delivery carriers have been developed in order to realize efficient gene-delivery, since such carriers can undergo physical or chemical reactions in response to changes in pH, oxidative state, or enzymatic activity. As these stimuli or cues may be specific to a biological site, tissue, or condition, it may facilitate the release of the nucleic acid cargo at the desired site in an efficient manner. Among all these stimuli-responsive carriers, pH-responsive one has attracted major attention and great impetus has been directed towards utilizing the subtle yet significant change in pH value within the cellular compartments. In this review, we give an overview of pH-sensitive lipids and polymers which have been designed and developed in recent years, with focus on their structural features and consequent functional attributes to achieve efficient transfection. The underlying modes of actions relating to structure and differential pH environment have also been discussed. It is worthy to note that despite many pH-sensitive carriers have shown success in vitro and a few in vivo, none have entered clinical phase for their transfection activity is still insufficient. To develop more efficient gene delivery carriers, the exact mechanisms of how these pH-sensitive carriers overcome each intracellular obstacle, as well as some concepts such as "proton sponge", have to be maken more clear or verified further.

Key words: gene therapy, gene delivery, nonviral gene carrier, pH-sensitive lipids, pH-sensitive polymers