Trichain cationic lipids: the potential of their lipoplexes for gene delivery.
Trichain cationic lipids: the potential of their lipoplexes for gene delivery.
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DOI：
10.1039/c8bm00965a
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发表时间：
2018-12-18
影响因子：
6.6
通讯作者：
Lawrence MJ
中科院分区：
文献类型：
--
作者：
Kudsiova L;Mohammadi A;Mustapa MFM;Campbell F;Welser K;Vlaho D;Story H;Barlow DJ;Tabor AB;Hailes HC;Lawrence MJ
由DNA、DOPE和二环氧乙基阳离子脂或它们的新型三链(TC)对应物制备了脂络合物(LDS)。由辅助脂质、二油酰基L-α-磷脂酰乙醇胺(DOPE)和双链(DC)氧乙基化阳离子脂质或相应的新型三链(TC)类似物组成的带正电荷的囊泡与脱氧核糖核酸(DNAs)制备了脂合物(LD)。这是首次将TC脂用于LDS的制备及其应用的研究。在这里，表征LDS的生物物理实验的结果已经与络合物的体外转导活性相关联。光子相关光谱、Zeta电位测量和透射电子显微镜研究表明，无论是否存在第三链，含LDS的TC和DC的尺寸和电荷几乎没有差异。然而，小角中子散射研究证实，当脂双层以LD复合体的形式存在时，与母体囊泡相反，存在显着的构象重排。这种重排在含有第三条C12链或更长链的TC脂类的LDS中尤其明显。这些结果表明，在DNA存在的情况下，第三疏水链的存在对脂质堆积有显著的影响。Picogreen荧光和凝胶电泳研究表明，含有至少C12的第三个酰基链的TC脂对DNA的络合效果最好，而含有辛酰链的TC脂和DC脂的络合效果最差。LDS形式的TC脂类的转染率高于DC类似物，尤其是当第三个酰基链是辛酰基或油酰基时。当第三链是甲基、乙酰基或十二烷基时，几乎或没有观察到转染率的增加。TC脂类在转染性能上的大幅提高可以归因于它们使其DNA有效载荷复杂化的能力。这些研究表明，中等或较长的第三个酰基链的存在特别有利于转染性。
Lipoplexes (LDs) have been prepared from DNA, DOPE and either a dichain oxyethylated cationic lipid or their novel trichain (TC) counterpart. Lipoplexes (LDs) have been prepared from DNA and positively charged vesicles composed of the helper lipid, dioleoyl l-α-phosphatidylethanolamine (DOPE) and either a dichain (DC) oxyethylated cationic lipid or their corresponding novel trichain (TC) counterpart. This is the first study using the TC lipids for the preparation of LDs and their application. Here the results of biophysical experiments characterising the LDs have been correlated with the in vitro transfection activity of the complexes. Photon correlation spectroscopy, zeta potential measurements and transmission electron microscopy studies indicated that, regardless of the presence of a third chain, there were little differences between the size and charge of the TC and DC containing LDs. Small angle neutron scattering studies established however that there was a significant conformational re-arrangement of the lipid bilayer when in the form of a LD complex as opposed to the parent vesicles. This re-arrangement was particularly noticeable in LDs containing TC lipids possessing a third chain of C12 or a longer chain. These results suggested that the presence of a third hydrophobic chain had a significant effect on lipid packing in the presence of DNA. Picogreen fluorescence and gel electrophoresis studies showed that the TC lipids containing a third acyl chain of at least C12 were most effective at complexing DNA while the TC lipids containing an octanoyl chain and the DC lipids were least effective. The transfection efficacies of the TC lipids in the form of LDs were found to be higher than for the DC analogues, particularly when the third acyl chain was an octanoyl or oleoyl moeity. Little or no increase in transfection efficiency was observed when the third chain was a methyl, acetyl or dodecanoyl group. The large enhancement in transfection performance of the TC lipids can be attributed to their ability to complex their DNA payload. These studies indicate that presence of a medium or long third acyl chain was especially beneficial for transfection.
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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
影响因子：
--
作者：
Kudsiova, Laila;Ho, Jimmy;Lawrence, M. Jayne
通讯作者：
Lawrence, M. Jayne
影响因子：
2.9
作者：
Merkle, D;Lees-Miller, SP;Cramb, DT
通讯作者：
Cramb, DT
影响因子：
3.4
作者：
Balgavy, P;Dubnicková, M;Uhriková, D
通讯作者：
Uhriková, D
盐水中的阳离子阳离子脂质体-DNA络合是途径依赖性的。
影响因子：
3.4
作者：
Silva, Bruno F. B.;Majzoub, Ramsey N.;Chan, Chia-Ling;Li, Youli;Olsson, Ulf;Safinya, Cyrus R.
通讯作者：
Safinya, Cyrus R.