A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival

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Bibliographische Detailangaben
Zeitschriftentitel:	Molecular Cancer Therapeutics
Personen und Körperschaften:	Mohanty, Suchismita, Chen, Zixin, Li, Kai, Morais, Goreti Ribeiro, Klockow, Jessica, Yerneni, Ketan, Pisani, Laura, Chin, Frederick T., Mitra, Siddharta, Cheshier, Samuel, Chang, Edwin, Gambhir, Sanjiv Sam, Rao, Jianghong, Loadman, Paul M., Falconer, Robert A., Daldrup-Link, Heike E.
In:	Molecular Cancer Therapeutics, 16, 2017, 9, S. 1909-1921
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	American Association for Cancer Research (AACR)
Schlagwörter:	Cancer Research Oncology

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Zusammenfassung:	<jats:title>Abstract</jats:title> <jats:p>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 with treatment with temozolomide alone. Thus, we present a novel therapeutic strategy with significant impact on survival and great potential for clinical translation. Mol Cancer Ther; 16(9); 1909–21. ©2017 AACR.</jats:p>
Umfang:	1909-1921
ISSN:	1535-7163 1538-8514
DOI:	10.1158/1535-7163.mct-17-0022