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首页> 外文期刊>International Journal of Nanomedicine >Elucidating the role of free polycationic chains in polycation gene carriers by free chains of polyethylenimine or N,N,N-trimethyl chitosan plus a certain polyplex
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Elucidating the role of free polycationic chains in polycation gene carriers by free chains of polyethylenimine or N,N,N-trimethyl chitosan plus a certain polyplex

机译：通过聚乙烯亚胺或N，N，N-三甲基壳聚糖与某些复合物的自由链阐明自由聚阳离子链在聚阳离子基因载体中的作用

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Abstract: Polycations as gene carriers have attracted considerable attention over the past decade. Generally, polyplexes between polycations and deoxyribonucleic acid (DNA) are formed at low N/P ratios (the ratios of the numbers of nitrogen atoms in a polycation to the numbers of phosphorus atoms in DNA), but high transfection efficiency can only be obtained at much higher N/P ratios. Thus, many polycationic chains are still free in solution. In this study, we investigated the detailed functions of free polyethylenimine chains (PEI-F) and free N,N,N-trimethyl chitosan chains (TMC-F) using the same polyplex, ie, TMC polyplex (TMC-P), which has high stability in Dulbecco’s Modified Eagle’s Medium (DMEM). Meanwhile, PEI polyplex (PEI-P)/PEI-F was also evaluated rather than PEI-P/TMC-F because the stability of PEI-P is low in DMEM and, in the latter case, the TMC-F may replace the bound PEI chain in PEI-P to form TMC-P. The transfection results show that both TMC-F and PEI-F can significantly increase the transfection efficiency of TMC-P; however, PEI-F can upregulate the gene expression of TMC-P more efficiently than TMC-F. Further investigations on the endocytosis and intracellular trafficking show that PEI-P/PEI-F, TMC-P/PEI-F, and TMC-P/TMC-F exhibit similar cellular uptake efficiency. However, by shutting down the clathrin-mediated endocytosis or vacuolar proton pump, the transfection efficiency decreases in the order of PEI-P/PEI-F > TMC-P/PEI-F > TMC-P/TMC-F. These findings indicate that PEI-F and TMC-F may promote the transfection efficiency of the polyplex by affecting its cellular uptake pathway and intracellular trafficking.
机译：摘要：在过去的十年中，聚阳离子作为基因载体受到了广泛的关注。通常，聚阳离子和脱氧核糖核酸（DNA）之间的多链体以低的N / P比（聚阳离子中的氮原子数与DNA中的磷原子数之比）形成，但只有在N / P比要高得多。因此，许多聚阳离子链在溶液中仍然自由。在这项研究中，我们使用相同的复合物，即TMC复合物（TMC-P），研究了游离聚乙烯亚胺链（PEI-F）和游离N，N，N-三甲基壳聚糖链（TMC-F）的详细功能。在Dulbecco的改良Eagle培养基（DMEM）中具有很高的稳定性。同时，也评估了PEI多态（PEI-P）/ PEI-F而不是PEI-P / TMC-F，因为DMEM中PEI-P的稳定性很低，在后一种情况下，TMC-F可能会取代PEI-P / TMC-F。将PEI-P中的PEI链结合形成TMC-P。转染结果表明，TMC-F和PEI-F均可显着提高TMC-P的转染效率。但是，PEI-F比TMC-F更有效地上调TMC-P的基因表达。对内吞作用和细胞内运输的进一步研究表明，PEI-P / PEI-F，TMC-P / PEI-F和TMC-P / TMC-F表现出相似的细胞摄取效率。但是，通过关闭网格蛋白介导的内吞作用或液泡质子泵，转染效率按PEI-P / PEI-F> TMC-P / PEI-F> TMC-P / TMC-F的顺序降低。这些发现表明，PEI-F和TMC-F可通过影响多态复合物的细胞摄取途径和细胞内运输来促进多态复合物的转染效率。

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