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dc.contributor.authorLiu, Xinrong
dc.contributor.authorNakamura, Kayoko
dc.contributor.authorCheng, Dengfeng
dc.contributor.authorPeng, Cong
dc.contributor.authorXiao, Nan
dc.contributor.authorLiu, Yuxia
dc.contributor.authorChen, Ling
dc.contributor.authorRusckowski, Mary
dc.contributor.authorHnatowich, Donald J.
dc.date2022-08-11T08:10:46.000
dc.date.accessioned2022-08-23T17:19:08Z
dc.date.available2022-08-23T17:19:08Z
dc.date.issued2012-07-01
dc.date.submitted2015-01-28
dc.identifier.citationCurr Drug Deliv. 2012 Jul;9(4):431-6. doi:10.2174/156720112801323035
dc.identifier.issn1567-2018 (Linking)
dc.identifier.doi10.2174/156720112801323035
dc.identifier.pmid22520071
dc.identifier.urihttp://hdl.handle.net/20.500.14038/48002
dc.description.abstractA three-component nanoparticle consisting of biotinylated Trastuzumab antiHer2 antibody, tat transferring peptide and radiolabeled antisense oligomer, linked together through streptavidin, have shown promise in the delivery to Her2+ tumor in mice following intravenous administration and with evidence of radiotherapeutic efficacy. These results have encouraged us to consider the nanoparticle as a delivery vehicle for RNA interference therapy in which the radiolabeled antisense oligomer is replaced with an unlabeled siRNA duplex. The siRNA stability within the nanoparticle was first confirmed by incubation with RNase A. The interferon responses, that indicate off-target cytotoxicity, were evaluated by quantitative real-time RT-PCR in BT-474 (Her2+) human breast cancer cells by measuring the mRNA expression of 2', 5'-oligoadenylate synthetase (OAS1) and Stat-1, two key interferon-responsive genes. Thereafter the cytotoxicity induced by the siRNA nanoparticle was evaluated by a clonogenic survival assay in BT-474 cells while the Her2 expression of these target cells was evaluated for evidence of specific gene silencing. The siRNA within the three-component anti- Her2/neu siRNA nanoparticle was largely protected from RNase-dependent degradation and did not activate an interferon response. The nanoparticle effectively and significantly inhibited colony formation of the target cells and silenced the Her2 gene expression at 5 nM compared with the identical nanoparticle with a scrambled siRNA. Our delivery nanoparticle, with tumor targeting provided by the antibody and its accumulation without entrapment, possibly due to the transfecting peptide, delivered an siRNA duplex to the proper subcellular localization for specific and effective gene silencing in culture by what appears to be an siRNA mechanism.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22520071&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.2174/156720112801323035
dc.subject2',5'-Oligoadenylate Synthetase
dc.subjectAntibodies, Monoclonal
dc.subjectAntibodies, Monoclonal, Humanized
dc.subjectBiotinylation
dc.subjectCell Line, Tumor
dc.subjectDrug Delivery Systems
dc.subjectFemale
dc.subject*Genes, erbB-2
dc.subjectHumans
dc.subjectInterferons
dc.subjectNanoparticles
dc.subjectRNA, Messenger
dc.subjectRNA, Small Interfering
dc.subjectReceptor, ErbB-2
dc.subjectSTAT1 Transcription Factor
dc.subjectStreptavidin
dc.subjectTransfection
dc.subjectdelivery nanoparticle
dc.subjectHer2
dc.subjectsiRNA
dc.subjectstreptavidin
dc.subjectradiolabeled oligomer
dc.subjectNanomedicine
dc.subjectNeoplasms
dc.subjectOncology
dc.subjectRadiology
dc.subjectTherapeutics
dc.titleHer2/neu small interfering RNA delivered in culture by a streptavidin nanoparticle
dc.typeJournal Article
dc.source.journaltitleCurrent drug delivery
dc.source.volume9
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/radiology_pubs/110
dc.identifier.contextkey6574749
html.description.abstract<p>A three-component nanoparticle consisting of biotinylated Trastuzumab antiHer2 antibody, tat transferring peptide and radiolabeled antisense oligomer, linked together through streptavidin, have shown promise in the delivery to Her2+ tumor in mice following intravenous administration and with evidence of radiotherapeutic efficacy. These results have encouraged us to consider the nanoparticle as a delivery vehicle for RNA interference therapy in which the radiolabeled antisense oligomer is replaced with an unlabeled siRNA duplex. The siRNA stability within the nanoparticle was first confirmed by incubation with RNase A. The interferon responses, that indicate off-target cytotoxicity, were evaluated by quantitative real-time RT-PCR in BT-474 (Her2+) human breast cancer cells by measuring the mRNA expression of 2', 5'-oligoadenylate synthetase (OAS1) and Stat-1, two key interferon-responsive genes. Thereafter the cytotoxicity induced by the siRNA nanoparticle was evaluated by a clonogenic survival assay in BT-474 cells while the Her2 expression of these target cells was evaluated for evidence of specific gene silencing. The siRNA within the three-component anti- Her2/neu siRNA nanoparticle was largely protected from RNase-dependent degradation and did not activate an interferon response. The nanoparticle effectively and significantly inhibited colony formation of the target cells and silenced the Her2 gene expression at 5 nM compared with the identical nanoparticle with a scrambled siRNA. Our delivery nanoparticle, with tumor targeting provided by the antibody and its accumulation without entrapment, possibly due to the transfecting peptide, delivered an siRNA duplex to the proper subcellular localization for specific and effective gene silencing in culture by what appears to be an siRNA mechanism.</p>
dc.identifier.submissionpathradiology_pubs/110
dc.contributor.departmentDepartment of Radiology, Division of Nuclear Medicine
dc.source.pages431-6


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