Targeted cellular ablation based on the morphology of malignant cells

dc.contributor.authorIvey, Jill W.en
dc.contributor.authorLatouche, Eduardo L.en
dc.contributor.authorSano, Michael B.en
dc.contributor.authorRossmeisl, John H. Jr.en
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.authorVerbridge, Scott S.en
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessioned2017-01-16T16:14:00Zen
dc.date.available2017-01-16T16:14:00Zen
dc.date.issued2015-11-24en
dc.description.abstractTreatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors.en
dc.description.versionPublished (Publication status)en
dc.format.extent? - ? (17) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/srep17157en
dc.identifier.issn2045-2322en
dc.identifier.urihttp://hdl.handle.net/10919/74343en
dc.identifier.volume5en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000365198400002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectnuclear-cytoplasmic ratioen
dc.subjectirreversible electroporationen
dc.subjectsingle-cellen
dc.subjectelectric-fieldsen
dc.subjectbrain-tumorsen
dc.subjectin-vitroen
dc.subjectintratumor heterogeneityen
dc.subject3d scaffoldsen
dc.subjectcancer-cellsen
dc.subjectglioblastomaen
dc.titleTargeted cellular ablation based on the morphology of malignant cellsen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/Engineering/Biomedical Engineering and Mechanicsen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Small Animal Clinical Sciencesen
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