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Phosphoester modified poly(ethylenimine) as efficient and low cytotoxic genevectors

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Abstract

Cyclic phosphoester monomer ethyl ethylene phosphate (EEP) modified poly(ethylenimine) (PEI), denoted as PEI-EEP, was developed for gene delivery. Three PEI-EEP polymers were synthesized and their structures were characterized by 1H and 31P NMR methods. All the PEI-EEP polymers could condense DNA efficiently at N/P ratios higher than 0.5/1. The physiochemical characteristics of PEI-EEP/DNA complexes were analyzed by particle size and zeta potential measurements. The particle sizes of complexes were around 160–250 nm, and their zeta potentials were around 30–45 mV at the N/P ratios ranging from 10/1 to 50/1. In vitro cell viability and transfection ability were evaluated in HEK293 and HeLa cells using PEI as the control. The cytotoxicity of PEI-EEP and PEI-EEP/DNA complexes was lower than that of PEI and its complexes with DNA. The transfection efficiency of PEI-EEP/DNA complexes was correlated to modification degrees with phosphoester. When the modification of phosphoester to PEI was moderate, the PEI-EEP1/DNA and PEI-EEP2/DNA complexes exhibited comparable or even higher transfection ability than PEI/DNA complex at its optimal N/P ratio in the absence of serum. However, transfection efficiency of PEI-EEP3 reduced dramatically. More importantly, the PEI-EEP exhibited higher transfection efficiency in the presence of 10% serum than that without serum. Therefore, PEI-EEP polymers may be attractive vectors for non-viral gene therapy.

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Authors and Affiliations

  1. Department of Polymer Science and Engineering, CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, 230026, China

    JinZhi Du

  2. Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China

    LingYan Tang, YouYong Yuan & Jun Wang

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  1. JinZhi Du
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  2. LingYan Tang
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  4. Jun Wang
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Correspondence to Jun Wang.

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Du, J., Tang, L., Yuan, Y. et al. Phosphoester modified poly(ethylenimine) as efficient and low cytotoxic genevectors. Sci. China Chem. 54, 351–358 (2011). https://doi.org/10.1007/s11426-010-4210-x

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