PEGylated cationic liposome-DNA complexation in brine is pathway-dependent.
PEGylated cationic liposome-DNA complexation in brine is pathway-dependent.
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盐水中的阳离子阳离子脂质体-DNA络合是途径依赖性的。
DOI：
10.1016/j.bbamem.2013.09.008
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发表时间：
2014-01
影响因子：
3.4
通讯作者：
Safinya, Cyrus R.
中科院分区：
文献类型：
--
作者：
Silva, Bruno F. B.;Majzoub, Ramsey N.;Chan, Chia-Ling;Li, Youli;Olsson, Ulf;Safinya, Cyrus R.
阳离子脂质体-DNA（CL-DNA）复合物被认为是安全、有效地递送基因用于治疗应用的有前途的材料。为了在体内使用，这些复合物可以用亲水性聚合物（例如聚乙二醇，PEG）包被，所述亲水性聚合物为蛋白质的粘附和免疫系统的去除提供空间稳定性。在这项工作中，我们研究了初始盐浓度（Cs）的影响-它调节带相反电荷的囊泡和DNA之间的静电相互作用-聚乙二醇化的CL-DNA颗粒的结构和稳定性。先前的小角X射线散射已经表明，如果在水中制备非聚乙二醇化或聚乙二醇化的CL-DNA层状复合物，则它们的结构由大量的脂质膜-DNA层（大于20）很好地限定。在这里，我们表明，如果这些复合物转移到盐水介质（150 mM NaCl或DMEM，都接近生理条件），这种结构几乎保持不变。相反，如果在盐水介质中制备PEG化复合物，则它们的层状结构松散得多，层数较少。PEG化复合物在盐水中形成的这种途径依赖性行为由脂质体膜电荷密度和膜中PEG 2000的摩尔分数调节，其中平均层数随着Cs的增加而减少，并且从5摩尔%到10摩尔%PEG-脂质。这些结构中的每一个（高层数和低层数）随时间稳定，表明尽管复合物形成在热力学上有利，但聚乙二醇化膜中的复合过程（其决定每个颗粒的层数）是动力学控制的。在极端情况下（当在低膜电荷密度下，来自10摩尔%PEG-脂质的聚合物排斥最大化并且PEG化CL和DNA之间的静电吸引最小化时），在高Cs=150 mM下抑制复合物形成。
Cationic liposome-DNA (CL-DNA) complexes, are regarded as promising materials for safe and efficient delivery of genes for therapeutical applications. In order to be used in vivo, these complexes may be coated with a hydrophilic polymer (e.g. polyethylene-glycol, PEG) that provides steric stabilization towards adhesion of proteins and removal by the immune system. In this work we study the influence of the initial salt concentration (Cs) – which modulates the electrostatic interaction between oppositely charged vesicles and DNA – on the structure and stability of PEGylated CL-DNA particles. Previous small-angle X-ray scattering has shown that if non-PEGylated or PEGylated CL-DNA lamellar complexes are prepared in water, their structure is well defined with a high number of lipid membrane-DNA layers (larger than 20). Here we show that if these complexes are transferred to saline media (150 mM NaCl or DMEM, both near physiological conditions), this structure remains nearly unchanged. Conversely, if PEGylated complexes are prepared in saline media, their lamellar structure is much looser, with fewer number of layers. This pathway dependent behavior of PEGylated complex formation in brine is modulated by the liposome membrane charge density and the mole fraction of PEG 2000 in the membranes, with the average number of layers decreasing with increasing Cs and in going from 5 mol% to 10 mol% PEG-lipid. Each of these structures (high and low number of layers) is stable with time, suggesting that despite complex formation being thermodynamically favored, the complexation process in PEGylated membranes, which determines the number of layers per particle, is kinetically controlled. In the extreme case (when polymer repulsions from 10 mol% PEG-lipid are maximized and electrostatic attraction between PEGylated CLs and DNA are minimized at low membrane charge density) complex formation is suppressed at high Cs=150 mM.
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DOI：
10.1021/la200450x
发表时间：
2011-06-07
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Golan S;Aytar BS;Muller JP;Kondo Y;Lynn DM;Abbott NL;Talmon Y
通讯作者：
Talmon Y
DOI：
10.1016/0005-2736(91)90246-5
发表时间：
1991-07-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ALLEN, TM;HANSEN, C;YAUYOUNG, A
通讯作者：
YAUYOUNG, A
DOI：
10.1073/pnas.85.18.6949
发表时间：
1988-09-01
影响因子：
11.1
作者：
GABIZON, A;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
DOI：
10.1038/mt.2011.190
发表时间：
2011-12
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
通讯作者：
--
影响因子：
14
作者：
Chan, Chia-Ling;Majzoub, Ramsey N.;Shirazi, Rahau S.;Ewert, Kai K.;Chen, Yen-Ju;Liang, Keng S.;Safinya, Cyrus R.
通讯作者：
Safinya, Cyrus R.