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dc.contributor.authorDeng, Zhou J.
dc.contributor.authorMorton, Stephen Winford
dc.contributor.authorBen-Akiva, Elana
dc.contributor.authorHammond, Paula T.
dc.contributor.authorDreaden, Erik Christopher
dc.contributor.authorShopsowitz, Kevin
dc.date.accessioned2016-02-12T20:55:37Z
dc.date.available2016-02-12T20:55:37Z
dc.date.issued2013-10
dc.date.submitted2013-08
dc.identifier.issn1936-0851
dc.identifier.issn1936-086X
dc.identifier.urihttp://hdl.handle.net/1721.1/101180
dc.description.abstractA single nanoparticle platform has been developed through the modular and controlled layer-by-layer process to codeliver siRNA that knocks down a drug-resistance pathway in tumor cells and a chemotherapy drug to challenge a highly aggressive form of triple-negative breast cancer. Layer-by-layer films were formed on nanoparticles by alternately depositing siRNA and poly-l-arginine; a single bilayer on the nanoparticle surface could effectively load up to 3500 siRNA molecules, and the resulting LbL nanoparticles exhibit an extended serum half-life of 28 h. In animal models, one dose via intravenous administration significantly reduced the target gene expression in the tumors by almost 80%. By generating the siRNA-loaded film atop a doxorubicin-loaded liposome, we identified an effective combination therapy with siRNA targeting multidrug resistance protein 1, which significantly enhanced doxorubicin efficacy by 4 fold in vitro and led to up to an 8-fold decrease in tumor volume compared to the control treatments with no observed toxicity. The results indicate that the use of layer-by-layer films to modify a simple liposomal doxorubicin delivery construct with a synergistic siRNA can lead to significant tumor reduction in the cancers that are otherwise nonresponsive to treatment with Doxil or other common chemotherapy drugs. This approach provides a potential strategy to treat aggressive and resistant cancers, and a modular platform for a broad range of controlled multidrug therapies customizable to the cancer type in a singular nanoparticle delivery system.en_US
dc.description.sponsorshipJanssen Pharmaceutical Ltd. (TRANSCEND Grant)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)en_US
dc.description.sponsorshipNational Health and Medical Research Council (Australia) (CJ Martin Fellowship)en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Graduate Research Fellowshipen_US
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship)en_US
dc.language.isoen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/nn4047925en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleLayer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatmenten_US
dc.typeArticleen_US
dc.identifier.citationDeng, Zhou J., Stephen W. Morton, Elana Ben-Akiva, Erik C. Dreaden, Kevin E. Shopsowitz, and Paula T. Hammond. “Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment.” ACS Nano 7, no. 11 (November 26, 2013): 9571–9584.en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.mitauthorDeng, Zhou J.en_US
dc.contributor.mitauthorMorton, Stephen Winforden_US
dc.contributor.mitauthorBen-Akiva, Elanaen_US
dc.contributor.mitauthorDreaden, Erik Christopheren_US
dc.contributor.mitauthorShopsowitz, Kevinen_US
dc.contributor.mitauthorHammond, Paula T.en_US
dc.relation.journalACS Nanoen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsDeng, Zhou J.; Morton, Stephen W.; Ben-Akiva, Elana; Dreaden, Erik C.; Shopsowitz, Kevin E.; Hammond, Paula T.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-4954-8443
dc.identifier.orcidhttps://orcid.org/0000-0003-3988-0837
mit.licensePUBLISHER_POLICYen_US


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