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dc.contributor.authorKelly, Kimberly A.
dc.contributor.authorShaw, Stanley Y.
dc.contributor.authorNahrendorf, Matthias
dc.contributor.authorKristoff, Kelly
dc.contributor.authorAikawa, Elena
dc.contributor.authorSchreiber, Stuart L.
dc.contributor.authorClemons, Paul A.
dc.contributor.authorWeissleder, Ralph
dc.date.accessioned2019-09-21T03:37:59Z
dc.date.issued2009
dc.identifier.citationKelly, Kimberly A., Stanley Y. Shaw, Matthias Nahrendorf, Kelly Kristoff, Elena Aikawa, Stuart L. Schreiber, Paul A. Clemons, and Ralph Weissleder. 2009. “Unbiased Discovery of in Vivo Imaging Probes through in Vitro Profiling of Nanoparticle Libraries.” Integrative Biology 1 (4): 311. https://doi.org/10.1039/b821775k.
dc.identifier.issn1757-9694
dc.identifier.issn1757-9708
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41384397*
dc.description.abstractIn vivo imaging reveals how proteins and cells function as part of complex regulatory networks in intact organisms, and thereby contributes to a systems-level understanding of biological processes. However, the development of novel in vivo imaging probes remains challenging. Most probes are directed against a limited number of pre-specified protein targets; cell-based screens for imaging probes have shown promise, but raise concerns over whether in vitro surrogate cell models recapitulate in vivo phenotypes. Here, we rapidly profile the in vitro binding of nanoparticle imaging probes in multiple samples of defined target vs. background cell types, using primary cell isolates. This approach selects for nanoparticles that show desired targeting effects across all tested members of a class of cells, and decreases the likelihood that an idiosyncratic cell line will unduly skew screening results. To adjust for multiple hypothesis testing, we use permutation methods to identify nanoparticles that best differentiate between the target and background cell classes. (This approach is conceptually analogous to one used for high-dimensionality datasets of genome-wide gene expression, e.g. to identify gene expression signatures that discriminate subclasses of cancer.) We apply this approach to the identification of nanoparticle imaging probes that bind endothelial cells, and validate our in vitro findings in human arterial samples, and by in vivo intravital microscopy in mice. Overall, this work presents a generalizable approach to the unbiased discovery of in vivo imaging probes, and may guide the further development of novel endothelial imaging probes.
dc.language.isoen_US
dc.publisherOxford University Press
dash.licenseLAA
dc.titleUnbiased discovery of in vivo imaging probes through in vitro profiling of nanoparticle libraries
dc.typeJournal Article
dc.description.versionAccepted Manuscript
dc.relation.journalIntegrative Biology
dash.depositing.authorWeissleder, Ralph::ea07ce19f187d4fab47c56ee97fa5c5a::600
dc.date.available2019-09-21T03:37:59Z
dash.workflow.comments1Science Serial ID 41103
dc.identifier.doi10.1039/b821775k
dash.source.volume1;4
dash.source.page311


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