Functional Delivery of siRNA in Mice Using Dendriworms

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dc.contributor.authorAgrawal, Amitko
dc.contributor.authorSingh, Neetuko
dc.contributor.authorZhu, Haihaoko
dc.contributor.authorBirjiniuk, Alonako
dc.contributor.authorvon Maltzahnko
dc.contributor.authorHarris, Todd J.ko
dc.contributor.authorXing, Deyinko
dc.contributor.authorWoolfenden, Stephen D.ko
dc.contributor.authorSharp, Phillip A.ko
dc.contributor.authorCharest, Alainko
dc.contributor.authorBhatia, Sangeetako
dc.contributor.authorMin, Dal-Heeko
dc.date.accessioned2013-03-09T12:06:25Z-
dc.date.available2013-03-09T12:06:25Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued2009-09-
dc.identifier.citationACS NANO, v.3, no.9, pp.2495 - 2504-
dc.identifier.issn1936-0851-
dc.identifier.urihttp://hdl.handle.net/10203/96302-
dc.description.abstractSmall interfering RNAs (siRNAs) mediate cleavage of specific, complementary mRNA sequences and thus regulate gene expression. Not surprisingly, their use for treatment of diseases that are rooted in aberrant gene expression, such as cancer, has become a paradigm that has gained wide interest. Here, we report the development of dendrimer-conjugated magnetofluorescent nanoworms that we call "dendriworms" as a modular platform for siRNA delivery in vivo. This platform maximizes endosomal escape to robustly produce protein target knockdown in vivo, and is tolerated well in mouse brain. We demonstrate that siRNA-carrying dendriworms can be readily internalized by cells and enable endosomal escape across a wide range of loading doses, whereas dendrimers or nanoworms alone are inefficient. Further, we show that dendriworms carrying siRNA against the epidermal growth factor receptor (EGFR) reduce protein levels of EGFR in human glioblastoma cells by 70-80%, 2.5-fold more efficiently than commercial cationic lipids. Dendriworms were well-tolerated after 7-days of convection-enhanced delivery to the mouse brain and in an EGFR-driven transgenic model of glioblastoma, anti-EGFR dendriworms led to specific and significant suppression of EGFR expression. Collectively,these data establish dendriworms as a multimodal platform that enables fluorescent tracking of siRNA delivery in vivo, cellular entry, endosomal escape, and knockdown of target proteins.-
dc.languageEnglish-
dc.publisherAMER CHEMICAL SOC-
dc.subjectGROWTH-FACTOR RECEPTOR-
dc.subjectIRON-OXIDE NANOPARTICLES-
dc.subjectRNA INTERFERENCE-
dc.subjectGLIOBLASTOMA-MULTIFORME-
dc.subjectGENE DELIVERY-
dc.subjectPOLYAMIDOAMINE DENDRIMERS-
dc.subjectGOLD NANOPARTICLES-
dc.subjectPAMAM DENDRIMERS-
dc.subjectMAMMALIAN-CELLS-
dc.subjectXENOGRAFT MODEL-
dc.titleFunctional Delivery of siRNA in Mice Using Dendriworms-
dc.typeArticle-
dc.identifier.wosid000269988600010-
dc.identifier.scopusid2-s2.0-70349551739-
dc.type.rimsART-
dc.citation.volume3-
dc.citation.issue9-
dc.citation.beginningpage2495-
dc.citation.endingpage2504-
dc.citation.publicationnameACS NANO-
dc.identifier.doi10.1021/nn900201e-
dc.contributor.localauthorMin, Dal-Hee-
dc.contributor.nonIdAuthorAgrawal, Amit-
dc.contributor.nonIdAuthorSingh, Neetu-
dc.contributor.nonIdAuthorZhu, Haihao-
dc.contributor.nonIdAuthorBirjiniuk, Alona-
dc.contributor.nonIdAuthorvon Maltzahn-
dc.contributor.nonIdAuthorHarris, Todd J.-
dc.contributor.nonIdAuthorXing, Deyin-
dc.contributor.nonIdAuthorWoolfenden, Stephen D.-
dc.contributor.nonIdAuthorSharp, Phillip A.-
dc.contributor.nonIdAuthorCharest, Alain-
dc.contributor.nonIdAuthorBhatia, Sangeeta-
dc.type.journalArticleArticle-
dc.subject.keywordAuthordendrimer-
dc.subject.keywordAuthorsiRNA-
dc.subject.keywordAuthornanoparticle-
dc.subject.keywordAuthorEGFR-
dc.subject.keywordAuthorglioblastoma-
dc.subject.keywordPlusGROWTH-FACTOR RECEPTOR-
dc.subject.keywordPlusIRON-OXIDE NANOPARTICLES-
dc.subject.keywordPlusRNA INTERFERENCE-
dc.subject.keywordPlusGLIOBLASTOMA-MULTIFORME-
dc.subject.keywordPlusGENE DELIVERY-
dc.subject.keywordPlusPOLYAMIDOAMINE DENDRIMERS-
dc.subject.keywordPlusGOLD NANOPARTICLES-
dc.subject.keywordPlusPAMAM DENDRIMERS-
dc.subject.keywordPlusMAMMALIAN-CELLS-
dc.subject.keywordPlusXENOGRAFT MODEL-
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