The nucleobase analogue 2-amino-6-chloropurine was modified on the surface of polyamidoamine (PAMAM) to construct a derivative AP-PAMAM, and then it was used as a gene carrier for miR-23b delivery to achieve the anti-tumor effects. The carrier AP-PAMAM could condense miR-23b into stable nanoparticles with a particle size of 97.3 nm (N/P ratio of 50), which was favorable for the cellular uptake of nanoparticles. Compared with PAMAM, AP-PAMAM exhibited an obviously enhanced transfection efficiency through the transfection assay of plasmids pEGFP-N3 and pGL-3. Using the human lung adenocarcinoma cell line A549 as a model, AP-PAMAM-mediated miR-23b delivery could achieve a stronger anti-proliferative effect than PAMAM/miR-23b. The inhibition of cell proliferation was elucidated to be associated with the apoptotic induction (apoptotic ratio of 23.2%) and S phase arrest owing to the decreased expression level of cyclin D1. Meanwhile, the AP-PAMAM-mediated miR-23b delivery could suppress the cell migration and invasion of cancer cells through wound healing and Transwell migration assays. In summary, the PAMAM derivative-mediated miR-23b delivery could be a promising strategy for achieving tumor gene therapy.

中文翻译：

---

核碱基修饰的聚酰胺酰胺介导的miR-23b传递抑制肺癌的增殖和迁移

在聚酰胺酰胺（PAMAM）的表面上修饰核碱基类似物2-氨基-6-氯嘌呤，以构建衍生物AP-PAMAM，然后将其用作miR-23b递送的基因载体，以达到抗肿瘤作用。载体AP-PAMAM可以将miR-23b浓缩成粒径为97.3 nm（N / P比为50）的稳定纳米颗粒，这有利于纳米颗粒的细胞吸收。与PAMAM相比，AP-PAMAM通过质粒pEGFP-N3和pGL-3的转染实验显示出明显提高的转染效率。使用人肺腺癌细胞系A549作为模型，AP-PAMAM介导的miR-23b递送比PAMAM / miR-23b可以实现更强的抗增殖作用。阐明了对细胞增殖的抑制与凋亡诱导（凋亡比为23）有关。2％）和S期阻滞是由于细胞周期蛋白D1的表达水平下降所致。同时，AP-PAMAM介导的miR-23b递送可通过伤口愈合和Transwell迁移分析抑制癌细胞的迁移和侵袭。总之，PAMAM衍生物介导的miR-23b传递可能是实现肿瘤基因治疗的有前途的策略。