Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells

阳离子碳硅烷树枝状聚合物及其 siRNA 复合物与 MCF-7 细胞的相互作用

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作者:Kamila Białkowska, Katarzyna Miłowska, Sylwia Michlewska, Paulina Sokołowska, Piotr Komorowski, Tania Lozano-Cruz, Rafael Gomez-Ramirez, Francisco Javier de la Mata, Maria Bryszewska

Abstract

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.

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