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

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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化学酶法合成胆固醇-g-聚(胺-酯)载体用于p53基因递送以抑制肿瘤细胞的增殖和迁移

DOI:
10.1039/c8nj02574f
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发表时间:
2018-08
期刊:
New J. Chem.
影响因子:
--
通讯作者:
Yan Yang
Yan Yang
中科院分区:
其他
文献类型:
--
作者:
Mengmeng Dong;Jiawen Chen;Jiebing Yang;Wei Jiang;Haobo Han;Quanshun Li;Yan Yang

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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.
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