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

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Abstract

An amphiphilic cholesterol-g-poly(amine-co-ester) synthesized via a chemoenzymatic route has been successfully applied as a carrier in p53 gene delivery. The carrier was shown to possess favorable plasmid binding and condensation ability with a hydrodynamic size and a zeta potential of 89.1 ± 1.8 nm and +9.1 ± 1.8 mV, respectively, at a mass ratio of 40. Using the human cervical carcinoma cell line HeLa as a model, carrier/p53 transfection has been demonstrated to improve the expression level of the p53 gene by qPCR and western blotting. After the successful p53 gene delivery, an obvious anti-proliferative effect was observed by the MTT method, Live/Dead staining and colony formation inhibition assays. The inhibition mechanism of cell proliferation was further shown to be associated with the induction of cell cycle arrest at the 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, as 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 to achieve p53-based gene therapy.

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

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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, Advance Article
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    Chemoenzymatic synthesis of a 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, Advance Article , DOI: 10.1039/C8NJ02574F

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