Article ID Journal Published Year Pages File Type
1944446 Biochimica et Biophysica Acta (BBA) - Biomembranes 2012 8 Pages PDF
Abstract

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.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (121 K)Download as PowerPoint slideHighlights► 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.

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