MicroRNAs have been identified as a promising tool in cancer gene therapy, and an efficient and safe gene carrier was significantly required in the clinical application of miRNAs. Herein, a polyethylenimine (PEI) derivative, N-isopropylacrylamide-modified PEI (namely PEN), was constructed through Michael addition and then employed as a carrier for miR-29a transfection. The carrier PEN has been demonstrated to possess favorable ability to condense miR-29a into stable nanoparticles and protect miR-29a against the nuclease degradation, using agarose gel retardation assay. Meanwhile, PEN exhibited excellent efficiency in miR-29a transfection demonstrated by flow cytometry and confocal laser scanning microscope. Further, the PEN-mediated miR-29a transfection could achieve an obvious anti-proliferative effect owing to the activation of cell apoptosis and the cell cycle arrest at G1 phase, using human lung adenocarcinoma cell line A549 as a model. In addition, PEN/miR-29a nanoparticles could suppress the migration and invasion of cancer cells measured by wound healing and Transwell migration assays. Overall, the PEN-mediated miR-29a transfection could be potentially employed as a useful approach to achieve cancer gene therapy.

MicroRNAs 已被确定为癌症基因治疗的有前途的工具，并且在 miRNAs 的临床应用中迫切需要一种高效、安全的基因载体。在此，通过迈克尔加成构建了聚乙烯亚胺（PEI）衍生物，N-异丙基丙烯酰胺修饰的PEI（即PEN），并将其用作miR-29a转染的载体。使用琼脂糖凝胶阻滞试验，载体 PEN 已被证明具有将 miR-29a 凝聚成稳定纳米颗粒并保护 miR-29a 免受核酸酶降解的有利能力。同时，通过流式细胞术和共聚焦激光扫描显微镜证明，PEN 在 miR-29a 转染中表现出优异的效率。更远，以人肺腺癌细胞系A549为模型，PEN介导的miR-29a转染由于激活细胞凋亡和细胞周期停滞在G1期，可达到明显的抗增殖作用。此外，PEN/miR-29a 纳米颗粒可以抑制通过伤口愈合和 Transwell 迁移测定测量的癌细胞的迁移和侵袭。总体而言，PEN 介导的 miR-29a 转染可能被用作实现癌症基因治疗的有用方法。