Impact of Lipid Substitution on Assembly and Delivery of siRNA by Cationic Polymers
Impact of Lipid Substitution on Assembly and Delivery of siRNA by Cationic Polymers
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DOI：
10.1002/mabi.201000402
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发表时间：
2011-05-12
影响因子：
4.6
通讯作者：
Uludag, Hasan
中科院分区：
文献类型：
--
作者：
Aliabadi, Hamidreza Montazeri;Landry, Breanne;Uludag, Hasan
报道了一种聚合物文库的特征，该文库旨在增强它们保护和将其核苷酸货物运送到细胞的能力。随着聚合物/siRNA重量比的增加，聚合物/siRNA复合物的Zeta-电位不断增加，并且在所有比例下，脂质修饰的聚合物：siRNA复合物的Zeta-电位都高于PEI2。当聚合物：siRNA的比例为1：1时，所有的脂质取代聚合物都显示出完全的保护作用。脂质修饰的聚合物显著增加了细胞对siRNA复合体的摄取，下调了GAPDH和P-gp(max.分别为66%和67%)。结果表明，低分子PEI的疏水修饰可以使这种原本无效的聚合物成为一种安全有效的细胞内siRNA递送和蛋白质沉默的递送系统。
Characterization of a polymer library engineered to enhance their ability to protect and deliver their nucleotide cargo to the cells is reported. The zeta-potential continuously increased with higher polymer: siRNA weight ratio, and the zeta-potential of lipid-modified polymers: siRNA complexes were higher than PEI2 at all ratios. At polymer: siRNA ratio of 1: 1, all lipid-substituted polymers showed complete protection against degradation. Lipid-modified polymers significantly increased the cellular uptake of siRNA complexes and down-regulation of GAPDH and P-gp (max. 66% and 67%, respectively). The results indicate that hydrophobic modification of low molecular PEI could render this otherwise ineffective polymer to a safe effective delivery system for intracellular siRNA delivery and protein silencing.