A Zwitterionic-Shielded Carrier with pH-Modulated Reversible Self-Assembly for Gene Transfection

Yuju Shih, Antoine Venault, Lemmuel L. Tayo, Sheng Han Chen, Akon Higuchi, Andre Deratani, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Damien Quemener, Yung Chang

研究成果: 雜誌貢獻期刊論文同行評審

17 引文 斯高帕斯(Scopus)

摘要

Cationic vectors are ideal candidates for gene delivery thanks to their capability to carry large gene inserts and their scalable production. However, their cationic density gives rise to high cytotoxicity. We present the proper designed core-shell polyplexes made of either poly(ethylene imine) (PEI) or poly(2-dimethylamino ethyl methacrylate) (PDMAEMA) as the core and zwitterionic poly(acrylic acid)-block-poly(sulfobetaine methacrylate) (PAA-b-PSBMA) diblock copolymer as the shell. Gel retardation and ethidium bromide displacement assays were used to determine the PEI/DNA or PDMAEMA/DNA complexation. At neutral pH, the copolymer serves as a protective shell of the complex. As PSBMA is a nonfouling block, the shell reduced the cytotoxicity and enhanced the hemocompatibility (lower hemolysis activity, longer plasma clotting time) of the gene carriers. PAA segments in the copolymer impart pH sensitivity by allowing deshielding of the core in acidic solution. Therefore, the transfection efficiency of polyplexes at pH 6.5 was better than at pH 7.0, from β-galactosidase assay, and for all PAA-b-PSBMA tested. These results were supported by more favorable physicochemical properties in acidic solution (zeta potential, particle size, and interactions between the polymer and DNA). Thus, the results of this study offer a potential route to the development of efficient and nontoxic pH-sensitive gene carriers.

原文???core.languages.en_GB???
頁(從 - 到)1914-1926
頁數13
期刊Langmuir
33
發行號8
DOIs
出版狀態已出版 - 28 2月 2017

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