Inderscience Publishers

Functionalised silica nanoparticles stable in serum–containing medium efficiently deliver siRNA targeting HIV–1 co–receptor CXCR4 in mammalian cells

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The development of non–viral DNA delivery systems using nanomaterials has attracted much research interest for its potential in biomedicine. However, for these new nanocarriers to be successfully used in therapeutic applications they have to overcome many barriers. Here, we report the development and characterisation of polyethyleneimine–modified tetramethylrhodamine–doped silica nanoparticles as a vehicle to deliver siRNA in the presence of serum. We have demonstrated that polyethyleneimine–modified tetramethylrhodamine–doped silica nanoparticles bind and protect siRNA against nuclease degradation and facilitate cellular uptake and intracellular delivery of the siRNA in HeLa–derived TZM–bl cells. The nanoparticles can penetrate TMZ–bl cells at concentrations as low as 1 µg/mL and can escape the lysosomal and endosomal cavities. Following delivery, the nanoparticles release active siRNA targeting the co–receptor CXCR4 for HIV–1 to achieve reduction in the targeted mRNA and protein expression. These nanoparticles are also non–toxic for the cells and are capable of carrying out all of these functions in the presence of serum, a characteristic that is critical if such nanoparticles are to be employed in any type of in vivo application.

Keywords: dye–doped silica nanoparticles, siRNA delivery, cellular uptake, gene silencing, HIV–1 co–receptor, TZM–bl cells, CXCR4, serum containing medium, nanomaterials, nanotechnology, functionalised silica nanoparticles, mammalian cells, non–viral DNA, DNA delivery systems, biomedicine, nanocarriers, polyethyleneimine, tetramethylrhodamine, HIV AIDS

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