کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1944446 | 1053211 | 2012 | 8 صفحه PDF | دانلود رایگان |
One of the major limitations in gene therapy is an inability of naked siRNA to passively diffuse through negatively charged cell membranes. Therefore, the siRNA transport into a cell requires efficient carriers. In this work we analyzed the charge-dependent interaction of the complexes of cationic carbosilane dendrimers (CBD) and anti-HIV siRNA (dendriplexes) with the model membranes — large unilamellar vesicles (LUV). We used the second generation of branched with CBD carbon–silicon bonds (CBD-CS) which are water-stable and that of oxygen–silicon bonds (CBD-OS) which are slowly hydrolyzed in aqueous solutions. The LUVs were composed of zwitterionic dimyristoylphosphatidylcholine (DMPC), negatively charged dipalmitoylphosphatidylglycerol (DPPG) and their mixture (DMPC/DPPG, molar ratio 7:3). The interaction of dendriplexes with LUVs affected both zeta potential and size of the vesicles. The changes of these values were larger for the negatively charged LUV. CBD-CS resulted in the decrease of zeta potential values to more negative ones, whereas an opposite effect took place for CBD-OS suggesting a different kind of interaction between LUVs and the dendriplexes. The results indicate that both CBD-CS and CBD-OS can be used for transport of siRNA into the cells. However, CBD-CS are preferred due to a better stability in water and improved bioavailability of siRNA on their surface.
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► Carbosilane dendrimers as carriers for anti-HIV siRNA (siGAG1) were evaluated.
► siRNA/dendrimer complexes were formed.
► Formed dendriplexes were interacting with lipid vesicles.
► Carbosilane dendrimers can be considered for delivery of siRNA into the target cells.
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1818, Issue 9, September 2012, Pages 2209–2216