Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Biomaterials. 2011 Sep;32(25):5889-99. doi: 10.1016/j.biomaterials.2011.04.079. Epub 2011 May 18.
The possibility of using non-viral gene delivery systems for the treatment of cancer is currently limited by their lower transfection efficacy compared to viral systems. On the basis that amino acids such as arginine, lysine and leucine were involved in enhancing DNA transportation into cells, we hypothesized that the grafting of these amino acids to the highly promising generation 3 diaminobutyric polypropylenimine (DAB) dendrimer would improve its transfection efficacy in cancer cells. In this work we demonstrated that the conjugation of arginine, lysine and leucine to the dendrimer led to an enhanced anti-proliferative activity of the polyplexes, by up to 47-fold for DAB-Lys in T98G cancer cells compared to the unmodified polyplex in vitro. In vivo, the intravenous administration of amino acid-bearing DAB polyplexes resulted in a significantly improved tumor gene expression, with the highest gene expression level observed after treatment with DAB-Lys polyplex. Arginine, lysine and leucine-bearing generation 3 polypropylenimine polymers are therefore highly promising gene delivery systems for gene transfection in tumors.
目前，非病毒基因传递系统用于癌症治疗的可能性受到其转染效率低于病毒系统的限制。基于精氨酸、赖氨酸和亮氨酸等氨基酸参与增强 DNA 向细胞内运输，我们假设将这些氨基酸接枝到极有前途的第三代二氨基丁基聚丙稀亚胺（DAB）树枝状聚合物上将提高其在癌细胞中的转染效率。在这项工作中，我们证明了将精氨酸、赖氨酸和亮氨酸接枝到树枝状聚合物上可使多聚物的抗增殖活性增强，与未经修饰的多聚物相比，在 T98G 癌细胞中，DAB-Lys 的活性增强了 47 倍。在体内，通过静脉给予带有氨基酸的 DAB 多聚物，可显著改善肿瘤的基因表达，在用 DAB-Lys 多聚物处理后观察到最高的基因表达水平。因此，带有精氨酸、赖氨酸和亮氨酸的第三代聚丙稀亚胺聚合物是用于肿瘤基因转染的很有前途的基因传递系统。
