期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 16, 期 -, 页码 8037-8048出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S329433
关键词
phenylboronic acid; polyamidoamine; tumor-targeting ability; siPlk-1; gene therapy
资金
- National Key R&D Program of China [2020YFA0907003]
- National Natural Science Foundation of China [32071267, 81872928]
- Science and Technology Department of Jilin Province [20190201288JC]
- Development and Reform Commission of Jilin Province [2021C041-4]
- Interdisciplinary Innovation Program of Jilin University [JLUXKJC2020308]
The phenylboronic acid-modified polyamidoamine (PP) was used as a carrier for delivering Polo-like kinase-1 siRNA, leading to a significant anti-tumor response in hepatocarcinoma cells. The PP/siPlk-1 nanoparticles exhibited strong anti-proliferation effects and could efficiently suppress the migration and invasion of tumor cells. The derivative PP holds great potential as an ideal tumor-targeting carrier for gene therapy in malignant tumors.
Background: The construction of tumor-targeting carriers with favorable transfection efficiency was of great significance to achieve the tumor gene therapy. The phenylboronic acid-modified polyamidoamine (namely PP) was employed as a carrier for the delivery of Polo-like kinase-1 siRNA (siPlk-1), inducing an obvious anti-tumor response. Materials and Methods: The interaction between PP and siPlk-1 was evaluated by gel retardation assay. The transfection efficiency and tumor-targeting ability were analyzed by flow cytometry and confocal laser scanning microscopy, using hepatocarcinoma cell line HepG2 as a model. The anti-proliferation effect of PP/siPlk-1 and related mechanism were studied using the strategies of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis and cell cycle arrest. The anti-migration effect induced by PP/ siPlk-1 delivery was assayed by wound healing and Transwell migration techniques. Finally, quantitative real-time PCR and Western blotting were performed to measure the expression level of Plk-1 and other key targets. Results: The derivative PP could achieve the condensation of siPlk-1 into stable nanoparticles at nitrogen/phosphate groups ratio (N/P ratio) of >3.0, and it could facilitate the transfection of siPk-1 in a phenylboronic acid-dependent manner. The PP/siPlk-1 nanoparticles exhibited obvious anti-proliferation effect owing to the gene silence of Plk-1, which was identified to be associated with the cell apoptosis and cell cycle arrest at G2 phase. Meanwhile, PP/siPlk-1 transfection could efficiently suppress the migration and invasion of tumor cells. Conclusion: The derivative PP has been demonstrated to be an ideal tumor-targeting carrier for the delivery of Plk-1 siRNA, exhibiting great potential in the gene therapy of malignant tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据