DNA interaction with catanionic vesicles

DNA interaction with catanionic vesicles
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DOI:
10.1021/jp020391z
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发表时间:
2002-12-05
影响因子:
3.3
通讯作者:
Miguel, MG
Miguel, MG
中科院分区:
化学3区
文献类型:
--
作者:
Dias, RS;Lindman, B;Miguel, MG

文献摘要

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dna -阳离子脂质体复合物作为基因传递的可能载体是目前一个重要的问题。在这项工作中,DNA与热力学稳定的,自发形成的,带净正电荷的阳离子囊泡之间的相互作用进行了研究。绘制了由CTAB(十六烷基三甲基溴化铵)和SOS(硫酸辛基钠)组成的DNA和带正电的囊泡水溶液体系的相图,结果表明,正如预期的那样,具有很强的结合相行为,并形成沉淀。在所有的研究浓度中都观察到一个两相区。当[DNA]/ [S+]的电荷比低于1.3时,我们通过光学显微镜和电子显微镜发现,未受干扰的囊泡和DNA-表面活性剂复合物共存。在DNA含量较高的样品中,溶液中只观察到DNA-囊泡复合物。利用小角x射线衍射(SAXS)和低温透射电镜(cro - tem)对这些配合物的结构进行了研究,发现它们是由两亲分子双层组成的短程片层结构,DNA分子在这些层之间有序排列。这种类型的结构已经在文献中被提到,是dna -脂质体混合物中最常见的结构,并且表明我们使用的囊泡在制备和稳定性方面具有主要优势,具有相似的行为,因此可以成功地用作模型系统。然而,与先前研究的系统相比,我们观察到一个有趣的差异。因此,向样品中添加过量的DNA不会像之前观察到的那样导致DNA-囊泡复合物和DNA共存,而是导致复合物中可能包含过量的DNA,从而导致复合物和从双层中排出的阴离子表面活性剂胶束共存。
DNA-cationic liposome complexes as possible vehicles for gene delivery is currently an important issue. In this work, the interaction between DNA and thermodynamically stable, spontaneously formed, catanionic vesicles with a net positive charge is studied. A phase map was drawn for the aqueous system of DNA and positively charged vesicles, composed of CTAB (cetyltrimethylammonium bromide) and SOS (sodium octyl sulfate), and showed, as expected, a strong associative phase behavior with the formation of a precipitate. A two-phase region was observed over all the studied concentrations. For DNA-surfactant mixing ratios, [DNA]/ [S+] below 1.3 by charge, we found, by optical and electron microscopy, a coexistence between undisturbed vesicles and DNA-surfactant complexes. In samples with a higher excess of DNA, only DNA-vesicle complexes were observed, in solution. The structure of these complexes was studied by both small-angle X-ray diffraction (SAXS) and cryogenic transmission electron microscopy (cryo-TEM), and a short-range lamellar structure composed of amphiphile bilayers with DNA molecules ordered and packed between these stacks was found. This type of structure has already been mentioned in the literature as being the most frequently found structure for DNA-liposome mixtures and shows that the vesicles we used, having major advantages with respect to preparation and stability, have similar behavior and can thus be successfully used as model systems. We observed, however, an interesting difference in comparison with previously studied systems. Thus, the addition of DNA in excess to the samples leads not to the coexistence of DNA-vesicle complexes and DNA, as observed before, but to a probable inclusion of DNA in excess in the complexes and therefore to a coexistence of complexes and anionic surfactant micelles expelled from the bilayers.