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dc.contributor.authorMohanty, S.*
dc.contributor.authorChen, Z.*
dc.contributor.authorLi, K.*
dc.contributor.authorRibeiro Morais, Goreti*
dc.contributor.authorKlockow, J.*
dc.contributor.authorYerneni, K.*
dc.contributor.authorPasani, L.*
dc.contributor.authorChin, F.T.*
dc.contributor.authorMitra, S.*
dc.contributor.authorCheshier, S.*
dc.contributor.authorChang, E.*
dc.contributor.authorGambhir, S.S.*
dc.contributor.authorRao, J.*
dc.contributor.authorLoadman, Paul*
dc.contributor.authorFalconer, Robert A.*
dc.contributor.authorDaldrup-Link, H.E.*
dc.date.accessioned2017-07-04T10:57:14Z
dc.date.available2017-07-04T10:57:14Z
dc.date.issued2017-06
dc.identifier.citationMohanty S, Chen Z, Li K et al (2017) A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival. Molecular Cancer Therapeutics. 16(9): 1909-1921.
dc.identifier.urihttp://hdl.handle.net/10454/12440
dc.descriptionYes
dc.description.abstractGlioblastoma (GBM) has a dismal prognosis. Evidence from preclinical tumor models and human trials indicates the role of GBM initiating cells (GIC) in GBM drug resistance. Here, we propose a new treatment option with tumor enzyme-activatable, combined therapeutic and diagnostic (theranostic) nanoparticles, which caused specific toxicity against GBM tumor cells and GICs. The theranostic cross-linked iron oxide nanoparticles (CLIO) were conjugated to a highly potent vascular disrupting agent (ICT) and secured with a matrix-metalloproteinase (MMP-14) cleavable peptide. Treatment with CLIO-ICT disrupted tumor vasculature of MMP-14 expressing GBM, induced GIC apoptosis and significantly impaired tumor growth. In addition, the iron core of CLIO-ICT enabled in vivo drug tracking with MR imaging. Treatment with CLIO-ICT plus temozolomide achieved tumor remission and significantly increased survival of human GBM bearing mice by more than 2 fold compared to treatment with temozolomide alone. Thus, we present a novel therapeutic strategy with significant impact on survival and great potential for clinical translation.
dc.description.sponsorshipHeike E Daldrup-Link, NIH, R21CA176519 and R21CA190196; Sanjiv Sam Gambhir, NIH, 1U54CA199075; Jessica Klockow, NCI training grant, T32CA118681, Robert A. Falconer, University of Bradford, UoB-66031
dc.language.isoen
dc.rights© 2017 American Association for Cancer Research. Reproduced in accordance with the publisher's self-archiving policy.
dc.subjectGlioblastoma
dc.subjectGlioblastoma initiating cells
dc.subjectImaging
dc.subjectTherapy and theranostic nanoparticle
dc.titleA novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival
dc.status.refereedYes
dc.date.application2017-06-28
dc.typeArticle
dc.type.versionAccepted manuscript
dc.identifier.doihttps://doi.org/10.1158/1535-7163.MCT-17-0022
dc.rights.licenseUnspecified
refterms.dateFOA2018-07-25T16:09:33Z
dc.openaccess.statusopenAccess
dc.date.accepted2017-06-12


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