Mechanistic studies on aggregation of polyethylenimine-DNA complexes and its prevention
Mechanistic studies on aggregation of polyethylenimine-DNA complexes and its prevention
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DOI：
10.1002/bit.20444
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发表时间：
2005-06-05
影响因子：
3.8
通讯作者：
Klibanov, AM
中科院分区：
文献类型：
--
作者：
Sharma, VK;Thomas, M;Klibanov, AM
聚乙烯亚胺（PEI）-DNA复合物的聚集严重破坏了它们用于将基因递送到哺乳动物细胞中的效用。在此，我们着手阐明这种有害现象的机制，并制定合理的战略，以防止。温度，表面活性剂，复杂的浓度，离子强度，粘度和pH值的影响，这种聚集的时间过程进行了系统的研究。聚氧乙烯（100）硬脂酸酯（POES）的2.5%，并在较小程度上由其他非离子表面活性剂的聚集过程中完全抑制。重要的是，POES保留了复合物的转染效率而不诱导毒性。降低温度和pH值，稀释复合物，增加溶液粘度也减少了聚集。它的结论是，PEI-DNA复合物的聚集主要是由于疏水相互作用，而静电吸引起作用不大。(c)2005 Wiley Periodicals，Inc.
Aggregation of polyethylenimine (PEI)-DNA complexes severely undermines their utility for gene delivery into mammalian cells. Herein we undertook to elucidate the mechanism of this deleterious phenomenon and to develop rational strategies for its prevention. The effect of temperature, surfactants, complex concentration, ionic strength, viscosity, and pH on the time course of this aggregation was systematically examined. The aggregation process was completely inhibited by 2.5% polyoxyethylene (100) stearate (POES) and to a lesser degree by other nonionic surfactants. Importantly, POES preserved the transfection efficiency of the complexes without inducing toxicity. The aggregation was also reduced by lowering the temperature and pH, diluting the complexes, and increasing the solution viscosity. It is concluded that PEI-DNA complexes aggregate primarily due to hydrophobic interactions, while electrostatic attractions play little role. (c) 2005 Wiley Periodicals, Inc.