The tight binding of pDNA with a cationic polymer is the crucial requirement that prevents DNA degradation from undesired DNase attack to safely deliver the pDNA to its target site. However, cationic polymer-mediated strong gene holding limits pDNA dissociation from the gene complex, resulting in a reduction in transfection efficiency. In this study, to control the decomplexation rate of pDNA from the gene complex in a hard-to-transfect cell or an easy-to-transfect cell, either α-poly(l-lysine) (APL) or ε-poly(l-lysine) (EPL) was incorporated into branched polyethylenimine (bPEI)-based nanocomplexes (NCs). Compared to bPEI/pDNA NCs, the addition of APL or EPL formed smaller bPEI-APL/pDNA NCs with similar zeta potentials or larger bPEI-EPL/pDNA NCs with reduced zeta potentials, respectively, due to the different characteristics of the primary amines in the two poly(l-lysine)s (PLs). Interestingly, although both bPEI-APL/pDNA NCs and bPEI-EPL/pDNA NCs showed similar pDNA compactness to bPEI/pDNA NCs, the addition of APL or EPL resulted in slower or faster pDNA release, respectively, from the bPEI-PL/pDNA NCs than from the bPEI/pDNA NCs. bPEI-EPL/pDNA NCs with a decomplexation enhancer (i.e., EPL) improved the transfection efficiency (TE) in both a hard-to-transfect HepG2 cell and an easy-to-transfect HEK293 cell. However, although a decomplexation inhibitor (i.e., APL) reduced the TE of bPEI-APL/pDNA NCs in both cells, the degree of reduction in the TE could be compensated by PL-mediated enhanced nuclear delivery, particularly in HepG2 cells but not HEK293 cells, because both PLs facilitate nuclear localization of the gene complex per its cellular uptake. In conclusion, a decomplexation rate controller could be a potential factor to establish a high TE and design clinically available gene complex systems.

中文翻译：

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解复速率对易转染细胞或难转染细胞中以α-聚（l-赖氨酸）或ε-聚（l-赖氨酸）为解链控制因子的三元基因复合体转染的影响。

pDNA与阳离子聚合物的紧密结合是防止DNA因不希望的DNase攻击而降解的关键要求，以安全地将pDNA传递至其靶位点。但是，阳离子聚合物介导的强基因保持限制了pDNA从基因复合物中的解离，导致转染效率降低。在这项研究中，为了控制难于转染的细胞或易于转染的细胞（α-聚（1-赖氨酸）（APL）或ε）中pDNA从基因复合物中的解聚速率-聚（1-赖氨酸）（EPL）被合并到基于支链聚乙烯亚胺（bPEI）的纳米复合物（NCs）中。与bPEI / pDNA NCs相比，添加APL或EPL分别形成较小的bPEI-APL / pDNA NCs（具有相似的Zeta电位）或较大的bPEI-EPL / pDNA NCs（由于zeta电位降低），这是由于两个聚（1-赖氨酸）（PLs）。有趣的是，尽管bPEI-APL / pDNA NCs和bPEI-EPL / pDNA NCs都显示出与bPEI / pDNA NCs类似的pDNA紧实度，但是添加APL或EPL导致分别从bPEI-PL / pDNA释放较慢或更快的pDNA NCs比来自bPEI / pDNA NCs的NCs高。具有解复合增强剂（即EPL）的bPEI-EPL / pDNA NCs在难以转染的HepG2细胞和易于转染的HEK293细胞中均提高了转染效率（TE）。然而，尽管解复合抑制剂（即APL）降低了两种细胞中bPEI-APL / pDNA NCs的TE，但TE的降低程度可以通过PL介导的核传递增强来补偿，尤其是在HepG2细胞而非HEK293细胞中，因为两个PL都通过细胞吸收促进基因复合物的核定位。总之，解复合速率控制器可能是建立高TE并设计临床可用的基因复杂系统的潜在因素。