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Chemoenzymatic synthesis of cholesterol-g-poly(amine-co-ester) carrier for p53 gene delivery to inhibit the proliferation and migration of tumor cells

Abstract

An amphiphilic cholesterol-g-poly(amine-co-ester) synthesized in a chemoenzymatic route has been successfully applied as a carrier in p53 gene delivery. The carrier was identified to possess favorable plasmid binding and condensation ability with hydrodynamic size and zeta potential of 89.1  1.8 nm and +9.1  1.8 mV at a mass ratio of 40, respectively. Using human cervical carcinoma cell line HeLa as a model, carrier/p53 transfection has been demonstrated to improve the expression level of p53 gene by qPCR and Western blotting. After the successful p53 gene delivery, obvious anti-proliferative effect was observed by MTT method, Live/Dead staining and colony formation inhibition assays. The inhibition mechanism of cell proliferation was further discussed to be associated with the induction of cell cycle arrest at S phase and cell apoptosis through the activation of the mitochondria-dependent signaling pathway. Finally, the migration of tumor cells was restrained after p53 transfection elucidated by wound healing and Transwell migration assays. In summary, cholesterol-g-poly(amine-co-ester)-mediated p53 gene transfection could be a potential route for achieving the p53-based gene therapy.

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Publication details

The article was received on 24 May 2018, accepted on 07 Jul 2018 and first published on 09 Jul 2018


Article type: Paper
DOI: 10.1039/C8NJ02574F
Citation: New J. Chem., 2018, Accepted Manuscript
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    Chemoenzymatic synthesis of cholesterol-g-poly(amine-co-ester) carrier for p53 gene delivery to inhibit the proliferation and migration of tumor cells

    M. Dong, J. Chen, J. Yang, W. Jiang, H. Han, Q. Li and Y. Yang, New J. Chem., 2018, Accepted Manuscript , DOI: 10.1039/C8NJ02574F

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