Structure-activity relationships of poly(L-lysines):: effects of pegylation and molecular shape on physicochemical and biological properties in gene delivery
Structure-activity relationships of poly(L-lysines):: effects of pegylation and molecular shape on physicochemical and biological properties in gene delivery
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DOI：
10.1016/s0168-3659(02)00178-5
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发表时间：
2002-09-18
影响因子：
10.8
通讯作者：
Urtti, A
中科院分区：
文献类型：
--
作者：
Männistö, M;Vanderkerken, S;Urtti, A
研究了线型、接枝、树枝状和支化聚赖氨酸的形状、分子量和PEG化对其DNA递送性能的影响。测定DNA结合、凝聚、复合物大小和形态、细胞摄取和转染效率。大多数聚赖氨酸使DNA缩合，线性聚合物比大多数树枝状聚合物更有效。在低分子量的PLL DNA结合和缩合是不太有效的，特别是与树枝状聚合物。PEG化在低于60%（M-w分数）的PEG下不降低PLL的DNA缩合。聚乙二醇化在空间上稳定了复合物，但并没有保护它们免受与聚阴离子硫酸软骨素的相互作用。多聚赖氨酸/DNA复合物的细胞摄取是高的，并且聚乙二醇化增加了转染功效。然而，多聚赖氨酸的总体转染水平较低，可能是由于复合物从内体的逃逸不充分或DNA从复合物的释放较差。多聚赖氨酸的理化和生物结构与性质的关系得到了证实，但所测试的理化决定因素（复合物的大小，zeta电位，DNA的缩合和复合物的形状）和生物活性之间没有明显的相关性。转染活性最终可能由细胞内因素和/或DNA与载体复合的未知特征决定。(C)2002爱思唯尔科技有限公司。保留所有权利。
The influence of shape, molecular weight and pegylation of linear, grafted, dendritic and branched poly-L-lysines on their DNA delivery properties were investigated. DNA binding, condensation, complex size and morphology, cell uptake and transfection efficiency were determined. Most polylysines condense DNA, linear polymers being more efficient than most dendritic ones. At low molecular weights of PLL DNA binding and condensation were less efficient, particularly with dendrimers. Pegylation did not decrease DNA condensation of PLLs at less than 60% (fraction of M-w) of PEG. Pegylation stabilized the complexes sterically, but did not protect them from interaction with polyanionic chondroitin sulfate. Cell uptake of polylysine/DNA complexes was high and pegylation increased the transfection efficacy. However, overall transfection level of polylysines is low possibly due to inadequate escape of the complexes from endosomes or poor release of DNA from the complexes. Physicochemical and biological structure-property relationships Of poly-L-lysines were demonstrated, but no clear correlations between the tested physicochemical determinants (size of complexes, zeta-potentials, condensation of DNA and the shape of complexes) and biological activities were seen. Transfection activity may be ultimately determined by intracellular factors and/or still unknown features of DNA complexation with the carriers. (C) 2002 Elsevier Science B.V. All rights reserved.