International Journal of Nanomedicine (Dec 2021)
Phenylboronic Acid-Modified Polyamidoamine Mediated the Transfection of Polo-Like Kinase-1 siRNA to Achieve an Anti-Tumor Efficacy
Abstract
Gu Gong,1,* Xiuhui Tang,2,* Jiayuan Zhang,2 Xiao Liang,2 Jiebing Yang,2 Quanshun Li2 1Department of Orthopaedic Surgery, China-Japan Union Hospital, Jilin University, Changchun, 130031, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quanshun Li; Jiebing Yang Tel/Fax +86-431-85155200Email [email protected]; [email protected]: 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.Keywords: phenylboronic acid, polyamidoamine, tumor-targeting ability, siPlk-1, gene therapy
