Wang Mingxing, Wu Bo, Tucker Jason D, Lu Peijuan, Lu Qilong
McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, 1000 Blythe Blvd., Charlotte, NC 28231, USA.
J Mater Chem B. 2017 Jun 7;5(21):3907-3918. doi: 10.1039/c6tb03311c. Epub 2017 May 10.
A set of triazine-cored cationic amphiphilic polymers (TAPs) composed of low molecular weight (Mw) polyethylenimine (LPEI, B) and amphiphilic Jeffamine (A) were prepared with controllable composition and molecular size, and further characterized for plasmid DNA (pDNA) delivery both in vitro and in vivo. These new polymers condensed pDNA efficiently at a polymer/pDNA weight ratio of 5 with particle sizes below 200 nm. The introduction of Jeffamine in the polymers significantly improved the cellular uptake of pDNA, but without increasing its toxicity compared with the parent LPEI. The best formulation resulted in 6- and 29-fold transfection efficiencies of PEI 25k in vitro and in vivo in mdx mice, respectively. Higher transfection efficiency was achieved with more lipophilic A/A-based polymers in vitro, with 1A1B and 1A2B showing the greatest delivery performance. However, the lipophilicity of the TAPs is less critical in vivo as the less lipophilic A/A constructed TAPs also performed similarly well as the more lipophilic A/A constructed ones. In addition, a synergistic effect of LPEI and Jeffamine via chemical conjugation for the delivery of pDNA was revealed in transfection efficiency. These results indicate that the appropriate positive surface and particle size of polymer/pDNA complex and the composition and hydrophilic-lipophilic balance (HLB) of polymers are crucial for effective delivery, although intricate matching exists between A and B in the TAP composition. Triazine-cored cationic amphiphilic polymers are safe and potentially effective carriers for gene/drug delivery.
制备了一组由低分子量（Mw）聚乙烯亚胺（LPEI，B）和两亲性聚醚胺（A）组成的三嗪核阳离子两亲聚合物（TAPs），其组成和分子大小可控，并进一步对其在体外和体内递送质粒DNA（pDNA）的性能进行了表征。这些新型聚合物在聚合物/pDNA重量比为5时能有效地凝聚pDNA，粒径低于200nm。在聚合物中引入聚醚胺显著提高了pDNA的细胞摄取率，但与母体LPEI相比并未增加其毒性。最佳配方在体外和mdx小鼠体内的转染效率分别是PEI 25k的6倍和29倍。在体外，亲脂性更强的基于A/A的聚合物实现了更高的转染效率，其中1A1B和1A2B表现出最佳的递送性能。然而，TAPs的亲脂性在体内的影响较小，因为亲脂性较低的基于A/A构建的TAPs与亲脂性较高的基于A/A构建的TAPs表现同样良好。此外，在转染效率方面揭示了LPEI和聚醚胺通过化学共轭对pDNA递送的协同作用。这些结果表明，聚合物/pDNA复合物合适的正表面和粒径以及聚合物的组成和亲水-亲脂平衡（HLB）对于有效递送至关重要，尽管TAP组成中的A和B之间存在复杂匹配。三嗪核阳离子两亲聚合物是用于基因/药物递送的安全且潜在有效的载体。
