Wrobel Dominika, Kolanowska Katarzyna, Gajek Arkadiusz, Gomez-Ramirez Rafael, de la Mata Javier, Pedziwiatr-Werbicka Elżbieta, Klajnert Barbara, Waczulikova Iveta, Bryszewska Maria
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Biochim Biophys Acta. 2014 Mar;1838(3):882-9. doi: 10.1016/j.bbamem.2013.11.017. Epub 2013 Dec 5.
We have investigated the interactions between cationic NN16 and BDBR0011 carbosilane dendrimers with red blood cells or their cell membranes. The carbosilane dendrimers used possess 16 cationic functional groups. Both the dendrimers are made of water-stable carbon-silicon bonds, but NN16 possesses some oxygen-silicon bonds that are unstable in water. The nucleic acid used in the experiments was targeted against GAG-1 gene from the human immunodeficiency virus, HIV-1. By binding to the outer leaflet of the membrane, carbosilane dendrimers decreased the fluidity of the hydrophilic part of the membrane but increased the fluidity of the hydrophobic interior. They induced hemolysis, but did not change the morphology of the cells. Increasing concentrations of dendrimers induced erythrocyte aggregation. Binding of short interfering ribonucleic acid (siRNA) to a dendrimer molecule decreased the availability of cationic groups and diminished their cytotoxicity. siRNA-dendrimer complexes changed neither the fluidity of biological membranes nor caused cell hemolysis. Addition of dendriplexes to red blood cell suspension induced echinocyte formation.
我们研究了阳离子型NN16和BDBR0011碳硅烷树枝状大分子与红细胞或其细胞膜之间的相互作用。所使用的碳硅烷树枝状大分子具有16个阳离子官能团。这两种树枝状大分子均由水稳定的碳 - 硅键构成,但NN16含有一些在水中不稳定的氧 - 硅键。实验中使用的核酸靶向人类免疫缺陷病毒HIV - 1的GAG - 1基因。通过与膜的外层小叶结合,碳硅烷树枝状大分子降低了膜亲水部分的流动性,但增加了疏水内部的流动性。它们诱导了溶血,但没有改变细胞的形态。树枝状大分子浓度的增加诱导了红细胞聚集。短干扰核糖核酸(siRNA)与树枝状大分子分子的结合降低了阳离子基团的可用性并减弱了它们的细胞毒性。siRNA - 树枝状大分子复合物既没有改变生物膜的流动性,也没有引起细胞溶血。向红细胞悬液中添加树枝状复合物诱导了棘红细胞的形成。