Polyglutamic acid based polyanionic shielding system for polycationic gene carriers |
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Authors: | Jia-liang Xia Hua-yu Tian Jie Chen Zhao-pei Guo Lin Lin Hong-yan Yang Zong-cai Feng |
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Institution: | 1. School of Chemistry and Chemical Engineering,Lingnan Normal University,Zhanjiang 524048,China;Research Center of Chemistry & Materials,Lingnan Normal University,Development Center for New Materials Engineering & Technology in Universities of Guangdong,Zhanjiang 514048,China;2. Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Science,Changchun 130022,China;3. School of Chemistry and Chemical Engineering,Lingnan Normal University,Zhanjiang 524048,China |
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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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Keywords: | Gene delivery Shielding system PEGylation pH Sensitive |
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