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dc.contributor.authorChoi, Ki Young
dc.contributor.authorCorrea Echavarria, Santiago
dc.contributor.authorMin, Jouha
dc.contributor.authorLi, Jiahe
dc.contributor.authorRoy, Sweta
dc.contributor.authorLaccetti, Kristiana H
dc.contributor.authorDreaden, Erik
dc.contributor.authorKong, Stephanie
dc.contributor.authorHeo, Roun
dc.contributor.authorRoh, Young Hoon
dc.contributor.authorLawson, Edward C.
dc.contributor.authorPalmer, Peter A.
dc.contributor.authorHammond, Paula T
dc.date.accessioned2020-06-15T18:02:39Z
dc.date.available2020-06-15T18:02:39Z
dc.date.issued2019-03
dc.date.submitted2019-02
dc.identifier.issn1616-301X
dc.identifier.issn1616-3028
dc.identifier.urihttps://hdl.handle.net/1721.1/125799
dc.description.abstractUsing siRNA therapeutics to treat hematologic malignancies has been unsuccessful because blood cancer cells exhibit remarkable resistance to standard transfection methods. Herein, the successful delivery of siRNA therapeutics with a dual-targeted, layer-by-layer nanoparticle (LbL-NP) is reported. The LbL-NP protects siRNA from nucleases in the bloodstream by embedding it within polyelectrolyte layers that coat a polymeric core. The outermost layer consists of hyaluronic acid (a CD44-ligand) covalently conjugated to CD20 antibodies. The CD20/CD44 dual-targeting outer layer provides precise binding to blood cancer cells, followed by receptor-mediated endocytosis of the LbL-NP. This siRNA delivery platform is used to silence B-cell lymphoma 2 (BCL-2), a pro-survival protein, in vitro and in vivo. The dual-targeting approach significantly enhances internalization of BCL-2 siRNA in lymphoma and leukemia cells, which leads to significant downregulation of BCL-2 expression. Systemic administration of the dual-targeted, siRNA-loaded nanoparticle induces apoptosis and hampers proliferation of blood cancer cells, both in cell culture and in orthotopic non-Hodgkin's lymphoma animal models. These results provide the basis for approaches to targeting blood-borne cancers and other diseases and suggest that LbL nanoassemblies are a promising approach for delivering therapeutic siRNA to hematopoetic cell types that are known to evade transfection by other means.en_US
dc.language.isoen
dc.publisherWileyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1002/adfm.201900018en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourceProf. Hammond via Ye Lien_US
dc.titleBinary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticlesen_US
dc.typeArticleen_US
dc.identifier.citationChoi, Ki Young et al. "Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticles." Advanced Functional Materials 29, 20 (March 2019) © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheimen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.relation.journalAdvanced Functional Materialsen_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
dc.date.updated2020-06-08T16:49:44Z
dspace.date.submission2020-06-08T16:49:47Z
mit.journal.volume29en_US
mit.journal.issue20en_US
mit.licenseOPEN_ACCESS_POLICY


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