Polyglutamic Acid Based Polyanionic Shielding System for Polycationic Gene Carriers

Jia-liang Xia Hua-yu Tian Jie Chen Zhao-pei Guo Lin Lin Hong-yan Yang Zong-cai Feng

Citation:  Jia-liang Xia, Hua-yu Tian, Jie Chen, Zhao-pei Guo, Lin Lin, Hong-yan Yang, Zong-cai Feng. Polyglutamic Acid Based Polyanionic Shielding System for Polycationic Gene Carriers[J]. Chinese Journal of Polymer Science, 2016, 34(3): 316-323. doi: 10.1007/s10118-016-1756-x shu

Polyglutamic Acid Based Polyanionic Shielding System for Polycationic Gene Carriers

    通讯作者: Hua-yu Tian,
  • 基金项目:

    This work was financially supported by the National Natural Science Foundation of China (Nos. 51203132, 51222307, 51303173, 51390484, 21474104 and 51403205), Natural Science Foundation of Guangdong Province, China (S2012040008070) and Foundation for Distinguished Young Talents in Higher Education of Guangdong, China (2012LYM_0093).

摘要: For the purpose of increasing the in vivo stability of polycation gene carriers, we prepared a kind of pH-sensitive poly(ethylene glycol)-poly (-benzyl-L-glutamate-co-glutamic acid) (PEG-PGA(65), 65 denotes the molar ratio of glutamic acid in poly(-benzyl-L-glutamate-co-glutamic acid)). PEG-PGA(65) showed low cytotoxicity and could shield the positive charge of DNA/PEI (1:1) polyplexes efficiently. The transfection was enhanced due to the partially charge shielding in HeLa cell line at pH of 7.4. There was almost no transfection efficiency when the surface charge of the ternary particles turned to negative at pH of 7.4. However, the transfection efficiency recovered a lot by culturing at pH of 6.0 at the beginning of transfection. Confocal microscopic observation and flow cytometry results showed DNA/PEI polyplexes should be efficiently released and endocytosized at pH 6.0, because of the pH triggered deshielding action of PEG-PGA(65). Due to the good biocompatibility and suitable pH triggered shielding/deshielding property, PEG-PGA(65) could be a potential shielding system for polycationic gene carriers used in vivo.

English

  • 
    1. [1]

      Meredith, A.M. and Eric, E.S., Chem. Rev., 2009, 109(2): 259

    2. [2]

      Tian, H.Y., Chen, J. and Chen, X.S., Small, 2013, 9: 2034

    3. [3]

      Chen, J., Jiao, Z.X., Lin, L., Guo, Z.P., Tian H.Y. and Chen, X.S., Chinese J. Polym. Sci., 2015, 33(6): 830

    4. [4]

      Yin, H., Kanasty, R.L., Eltoukhy, A.A., Vegas, A.J., Dorkin J.R. and Anderson, D.G., Nat. Rev. Genet., 2014, 15: 541

    5. [5]

      Xu, C.H., Sui, M.H., Tang, J.B. and Shen, Y.Q., Chinese J. Polym. Sci., 2011, 29(3): 274

    6. [6]

      Tian, H.Y., Xiong, W., Wei, J.Z., Wang, Y., Chen, X.S., Jing, X.B. and Zhu, Q.Y., Biomaterials, 2007, 28(18): 2899

    7. [7]

      Qu, W., Chen, S., Ren, S., Jiang, X.J,. Zhuo, R.X. and Zhang, X.Z., Chinese J. Polym. Sci., 2013, 31(5): 713

    8. [8]

      Du, J., Tang, L.Y., Yuan, Y.Y. and Wang, J., Sci. China Chem., 2011, 54(2): 351

    9. [9]

      Tian, H.Y., Guo, Z.P., Chen, J., Lin, L., Xia, J.L., Dong, X. and Chen, X.S., Adv. Healthc. Mater. 2012, 1: 337

    10. [10]

      Zhang, B., Ma, X.P., Sui, M.H., Van, Kirk, E., Murdoch, W. J., Radosz, M., Lin, N.M. and Shen, Y.Q., Chinese J. Polym. Sci., 2015, 33(6): 908

    11. [11]

      Zhang, X., Pan, S.R., Hu, H.M.,Wu, G.F., Feng, M., Zhang, W. and Luo, X., J. Biomed. Mater. Res. A., 2008, 84(3): 795

    12. [12]

      Ogris, M., Brunner, S., Schuller, S., Kircheis, R. and Wagner, E., Gene Ther., 1999, 6: 595

    13. [13]

      Chen, L., Tian, H.Y., Chen, X.S., Park, T.G., Maruyama, A. and Jing, X.B., Acta Polymerica Sinica (in Chinese), 2009, (6): 499

    14. [14]

      Xia, J.L., Chen, L., Chen, J., Tian, H.Y., Li, F.F., Zhu, X.J., Li, G. and Chen, X.S., Macromol. Biosci., 2011, 11(2): 211

    15. [15]

      Xia, J.L., Tian, H.Y., Chen, L., Lin, L., Guo, Z.P., Chen, J. and Chen, X.S., Biomacromolecules, 2011, 12(4): 1024

    16. [16]

      Maruyama, K., Iwasaki, F., Takizawa, T., Yanagie, H., Niidome, T., Yamada, E., Ito, T. and Koyama, Y., Biomaterials, 2004, 25(16): 3267

    17. [17]

      Tian, H.Y., Lin, L., Chen, J., Chen, X.S., Park, T.G. and Maruyama, A., J. Control. Release, 2011, 155: 47

    18. [18]

      Xia, J.L., Chen, J., Tian, H.Y. and Chen, X.S., Sci. China Chem., 2010, 53(3): 502

    19. [19]

      Lee, E.S., Oh, K.T., Kim, D., Youn, Y.S. and Bae, Y.H., J. Control. Release, 2007, 123: 19

    20. [20]

      Yang, X.Z., Du, J.Z., Dou, S., Mao, C.Q., Long, H.Y. and Wang, J., ACS Nano., 2012, 6: 771

    21. [21]

      Shen, Y., Hu, G.X., Zhang, H.X., Qi, L.L. and Luo, C.C., Acta Chimica Sinica (in Chinese), 2013, 71: 323

    22. [22]

      Walker1, G.F., Ogris, M. and Wagner, E., Eur. J. Pharm. Sci., 2008, 34(4-5): 309

    23. [23]

      Knorr, V., Allmendinger, L., Walker, G.F., Paintner, F.F. and Wagner, E., Bioconjugate Chem., 2007, 18(4): 1218

    24. [24]

      Sethuraman, V.A., Na, K. and Bae, Y.H., Biomacromolecules, 2006, 7(1): 64

    25. [25]

      Lee, Y., Fukushima, S., Bae, Y.S., Hiki, S., Ishii, T. and Kataoka, K., J. Am. Chem. Soc., 2007, 129(17): 5362

    26. [26]

      Lee, Y., Miyata, K., Oba, M., Ishii, T., Fukushima, S., Han, M., Koyama, H., Nishiyama, N. and Kataoka, K., Angew. Chem. Int. Ed., 2008, 47(28): 5163

    27. [27]

      Poche, D.S., Moore, M.J. and Bowles, J.L., Synth. Commun., 1999, 29(5): 843

  • 加载中
计量
  • PDF下载量:  0
  • 文章访问数:  1336
  • HTML全文浏览量:  44
文章相关
  • 发布日期:  2016-03-05
  • 收稿日期:  2015-09-02
  • 修回日期:  2015-11-08
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章