A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival
dc.contributor.author | Mohanty, S. | * |
dc.contributor.author | Chen, Z. | * |
dc.contributor.author | Li, K. | * |
dc.contributor.author | Ribeiro Morais, Goreti | * |
dc.contributor.author | Klockow, J. | * |
dc.contributor.author | Yerneni, K. | * |
dc.contributor.author | Pasani, L. | * |
dc.contributor.author | Chin, F.T. | * |
dc.contributor.author | Mitra, S. | * |
dc.contributor.author | Cheshier, S. | * |
dc.contributor.author | Chang, E. | * |
dc.contributor.author | Gambhir, S.S. | * |
dc.contributor.author | Rao, J. | * |
dc.contributor.author | Loadman, Paul | * |
dc.contributor.author | Falconer, Robert A. | * |
dc.contributor.author | Daldrup-Link, H.E. | * |
dc.date.accessioned | 2017-07-04T10:57:14Z | |
dc.date.available | 2017-07-04T10:57:14Z | |
dc.date.issued | 2017-06 | |
dc.identifier.citation | Mohanty 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.uri | http://hdl.handle.net/10454/12440 | |
dc.description | Yes | |
dc.description.abstract | Glioblastoma (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.sponsorship | Heike 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.iso | en | |
dc.rights | © 2017 American Association for Cancer Research. Reproduced in accordance with the publisher's self-archiving policy. | |
dc.subject | Glioblastoma | |
dc.subject | Glioblastoma initiating cells | |
dc.subject | Imaging | |
dc.subject | Therapy and theranostic nanoparticle | |
dc.title | A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival | |
dc.status.refereed | Yes | |
dc.date.application | 2017-06-28 | |
dc.type | Article | |
dc.type.version | Accepted manuscript | |
dc.identifier.doi | https://doi.org/10.1158/1535-7163.MCT-17-0022 | |
dc.rights.license | Unspecified | |
refterms.dateFOA | 2018-07-25T16:09:33Z | |
dc.openaccess.status | openAccess | |
dc.date.accepted | 2017-06-12 |