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Issue 11, 2016
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PLL/PAE/DNA ternary complexes with enhanced endosomal escape ability for efficient and safe gene transfection

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Abstract

Three oligomeric linear poly(beta-amino esters) (PAEs) were synthesized and used to improve the gene transfection efficiency and reduce the cytotoxicity of poly(L-lysine) (PLL). The synthesized PAEs can co-assemble with PLL and plasmid DNA to form PLL/PAE/DNA ternary complexes of nanoscale sizes and moderate surface charges. The existence of multiple tertiary amines on PAE backbones imparts the ternary complexes with strong proton buffering capacity and therefore enhances the endosomal escape ability of the ternary complexes. In HeLa cells, the PLL/PAE/DNA ternary complexes show up to 476-fold enhancement in gene transfection efficiency when compared with the PLL/DNA binary complexes. Meanwhile, the incorporation of PAE oligomers significantly reduced the cytotoxicity of PLL. The strategy proposed here may provide insights into the development of PLL based gene delivery systems.

Graphical abstract: PLL/PAE/DNA ternary complexes with enhanced endosomal escape ability for efficient and safe gene transfection

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Publication details

The article was received on 24 Aug 2016, accepted on 30 Sep 2016 and first published on 03 Oct 2016


Article type: Paper
DOI: 10.1039/C6NJ02639G
Citation: New J. Chem., 2016,40, 9806-9812
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    PLL/PAE/DNA ternary complexes with enhanced endosomal escape ability for efficient and safe gene transfection

    Z. Sun and D. Zhou, New J. Chem., 2016, 40, 9806
    DOI: 10.1039/C6NJ02639G

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