Masotti A, Mossa G, Cametti C, Ortaggi G, Bianco A, Grosso N Del, Malizia D, Esposito C
Dipartimento di Chimica, Universita' di Roma "La Sapienza", Piazzale A. Moro n. 5, I-00185 Rome, Italy.
Colloids Surf B Biointerfaces. 2009 Feb 1;68(2):136-44. doi: 10.1016/j.colsurfb.2008.09.017. Epub 2008 Sep 25.
Lipid-DNA complexes (lipoplexes) are widely used, since several years, as gene carriers. However, their transfection efficiency, both in vitro and in vivo, depends, in a rather complex way, on different interconnected parameters, ranging from the chemical composition of the lipid components to the size and size distribution of the complexes and, moreover, to the composition of the suspending medium. In this paper, we have investigated the behavior of nine different commercially available transfection agents (liposomal and non-liposomal) and their lipoplexes, at different molar charge ratios and in different experimental conditions. The size and the time stability of the resulting lipoplexes were investigated by means of dynamic light scattering methods and their toxicity and transfection efficiency were assayed in vitro in a model tumor cell line (C6 rat glioma cell line). An attempt to correlate the different parameters governing the complex phenomenology observed has been made. Whereas all the formulations investigated display a low toxicity, that increases with the increase of the lipid-DNA molar charge ratio, the transfection efficiency markedly depends, besides the molar charge ratio, on the lipid composition and on the lipoplex size, in a rather correlated way. The aim of this work is to present, in a wide scenario, an example of the inter-correlation among the different parameters that influence the transfection efficiency of lipoplexes and to suggest the role exerted by the average size of the resulting aggregates in their overall effectiveness as carriers in gene therapy.
脂质 - DNA复合物（脂质体复合物）作为基因载体已被广泛使用多年。然而，它们在体外和体内的转染效率以一种相当复杂的方式取决于不同的相互关联参数，从脂质成分的化学组成到复合物的大小和大小分布，此外，还取决于悬浮介质的组成。在本文中，我们研究了九种不同的市售转染试剂（脂质体和非脂质体）及其脂质体复合物在不同摩尔电荷比和不同实验条件下的行为。通过动态光散射方法研究了所得脂质体复合物的大小和时间稳定性，并在体外模型肿瘤细胞系（C6大鼠胶质瘤细胞系）中测定了它们的毒性和转染效率。我们试图将控制所观察到的复杂现象学的不同参数联系起来。虽然所有研究的制剂都显示出低毒性，且毒性随着脂质 - DNA摩尔电荷比的增加而增加，但转染效率除了取决于摩尔电荷比外，还以一种相当相关的方式显著取决于脂质组成和脂质体复合物的大小。这项工作的目的是在广泛的情况下，展示影响脂质体复合物转染效率的不同参数之间相互关联的一个例子，并揭示所得聚集体的平均大小在其作为基因治疗载体的整体有效性中所起的作用。
