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Polyglutamic acid based polyanionic shielding system for polycationic gene carriers

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Abstract

For the purpose of increasing the in vivo stability of polycation gene carriers, we prepared a kind of pH-sensitive poly(ethylene glycol)-poly (γ-benzyl-L-glutamate-co-glutamic acid) (PEG-PGA(65), 65 denotes the molar ratio of glutamic acid in poly(γ-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.

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Lingnan Normal University, Zhanjiang, 524048, China

    Jia-liang Xia, Hong-yan Yang & Zong-cai Feng

  2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, 130022, China

    Hua-yu Tian  (田华雨), Jie Chen, Zhao-pei Guo & Lin Lin

  3. Research Center of Chemistry & Materials, Lingnan Normal University, Development Center for New Materials Engineering & Technology in Universities of Guangdong, Zhanjiang, 514048, China

    Jia-liang Xia & Zong-cai Feng

Authors
  1. Jia-liang Xia
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  2. Hua-yu Tian  (田华雨)
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  3. Jie Chen
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  4. Zhao-pei Guo
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  5. Lin Lin
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  6. Hong-yan Yang
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  7. Zong-cai Feng
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Corresponding author

Correspondence to Hua-yu Tian  (田华雨).

Additional information

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).

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Xia, Jl., Tian, Hy., Chen, J. et al. Polyglutamic acid based polyanionic shielding system for polycationic gene carriers. Chin J Polym Sci 34, 316–323 (2016). https://doi.org/10.1007/s10118-016-1756-x

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  • DOI: https://doi.org/10.1007/s10118-016-1756-x

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