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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\u2013expressing 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\u201321. \u00a92017 AACR.<\/jats:p>","DOI":"10.1158\/1535-7163.mct-17-0022","type":"journal-article","created":{"date-parts":[[2017,6,28]],"date-time":"2017-06-28T20:10:14Z","timestamp":1498680614000},"page":"1909-1921","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["A Novel Theranostic Strategy for\n                    <i>MMP-14<\/i>\n                    \u2013Expressing Glioblastomas Impacts Survival"],"prefix":"10.1158","volume":"16","author":[{"given":"Suchismita","family":"Mohanty","sequence":"first","affiliation":[{"name":"1Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California."}]},{"given":"Zixin","family":"Chen","sequence":"additional","affiliation":[{"name":"1Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California."}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[{"name":"1Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California."}]},{"given":"Goreti Ribeiro","family":"Morais","sequence":"additional","affiliation":[{"name":"2Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford, United Kingdom."}]},{"given":"Jessica","family":"Klockow","sequence":"additional","affiliation":[{"name":"1Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California."}]},{"given":"Ketan","family":"Yerneni","sequence":"additional","affiliation":[{"name":"3Department of Biology, Skidmore College, Saratoga Springs, New York."}]},{"given":"Laura","family":"Pisani","sequence":"additional","affiliation":[{"name":"1Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, 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Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California."},{"name":"5Department of Bioengineering, Stanford University, Stanford, California."},{"name":"6Department of Materials Science & Engineering, Stanford University, Stanford, California."}]},{"given":"Jianghong","family":"Rao","sequence":"additional","affiliation":[{"name":"1Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California."}]},{"given":"Paul M.","family":"Loadman","sequence":"additional","affiliation":[{"name":"2Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford, United Kingdom."}]},{"given":"Robert A.","family":"Falconer","sequence":"additional","affiliation":[{"name":"2Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford, United Kingdom."}]},{"given":"Heike 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