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

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DOIResolve DOI: http://doi.org/10.1504/IJNBM.2012.051704
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TypeArticle
Journal titleInternational Journal of Nano and Biomaterials
ISSN1752-8933
Volume4
Issue3/4
Pages223242; # of pages: 20
SubjectCellular uptake; CXCR4; Dye-doped silica nanoparticles; HIV-1 co-receptor; Serum-containing medium; siRNA delivery; Drug therapy; Genetic engineering; Nanoparticles; Nanostructured materials; chemokine receptor CXCR4; messenger RNA; nanoparticle; nuclease; polyethyleneimine; silicon dioxide; small interfering RNA; tetramethylrhodamine doped silica nanoparticle; cell viability; cellular distribution; chemical binding; endosome; enzyme degradation; gene silencing; human cell; Human immunodeficiency virus 1; lysosome; mammal cell; nonviral gene delivery system; protein expression; RNA binding; RNA degradation
AbstractThe 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 polyethyleneiminemodified 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. Copyright © 2012 Inderscience Enterprises Ltd.
Publication date
LanguageEnglish
AffiliationSecurity and Disruptive Technologies; National Research Council Canada
Peer reviewedYes
NPARC number21270095
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Record identifier4e9c3ab9-02ce-4980-b6bf-5f13d7a3ad09
Record created2013-12-23
Record modified2016-05-09
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