Abstract：
The impact of the molecular architecture on the transfection efficiency of PEGylated poly(amino acid) block copolymers was investigated for PEG-b-p(l-Lys)x -b-p(l-Leu)y , PEG-b-p(l-Leu)x -b-p(l-Lys)y , and PEG-b-p((l-Leu)x -co-(l-Lys)y ). The block lengths of p(l-Lys) and p(l-Leu) were varied between 10, 20, and 40; and 10 and 20, respectively, to study the influence of the ionic/hydrophobic balance. The results show that ABC triblock copolymers form smaller and more stable polyplexes with plasmid DNA than AB diblock copolymers-as verified by long-term aggregation and ethidium bromide exclusion studies-protect the DNA more effectively against nucleases, and provide better transfection efficiencies, as indicated by total protein as well as luciferase expression. More detailed studies revealed that triblock copolymers with p(l-Leu) forming the C-block were most efficient in DNA complexation with a 2.3 times higher transfection rate. Furthermore, increasing the cationic character by increasing the p(l-Lys) chain length led to up to 25% higher transfection but at the same time induced some cytotoxicity. Diblock copolymers, where the amino acid-building blocks exist as a random copolymer, bind more loosely with DNA leading to less compact and less stable aggregates with lower transfection efficiencies.
摘要：
对于PEG-b-p（l-Lys）x-b-p（l-Leu）y，研究了分子结构对聚乙二醇化聚（氨基酸）嵌段共聚物转染效率的影响。PEG-b-p(l-Leu)x-b-p(l-Lys)y,和PEG-b-p((l-Leu)x-co-(l-Lys)y)。p(l-Lys)和p(l-Leu)的嵌段长度在10、20和40之间变化；分别为10和20，研究离子/疏水平衡的影响。结果表明，ABC三嵌段共聚物比AB二嵌段共聚物与质粒DNA形成更小，更稳定的聚合复合物-如长期聚集和溴化乙锭排除研究所证实的-更有效地保护DNA免受核酸酶的侵害，并提供更好的转染效率，如总蛋白以及荧光素酶表达所示。更详细的研究表明,具有形成C-嵌段的p(l-Leu)的三嵌段共聚物在DNA复合中最有效,转染率高出2.3倍。此外，通过增加p(l-Lys)链长度来增加阳离子特性导致高达25%的更高转染,但同时诱导了一些细胞毒性。二嵌段共聚物，氨基酸结构单元以无规共聚物的形式存在，与DNA更松散地结合,导致具有较低转染效率的较不紧密和较不稳定的聚集体。
