American Association for Cancer Research
15357163mct170022-sup-177031_2_supp_4084457_zr50zx.docx (5.55 MB)

Figure S5 from A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival

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journal contribution
posted on 2023-04-03, 16:08 authored by Suchismita Mohanty, Zixin Chen, Kai Li, Goreti Ribeiro Morais, Jessica Klockow, Ketan Yerneni, Laura Pisani, Frederick T. Chin, Siddharta Mitra, Samuel Cheshier, Edwin Chang, Sanjiv Sam Gambhir, Jianghong Rao, Paul M. Loadman, Robert A. Falconer, Heike E. Daldrup-Link

Effect of CLIO-ICT on mouse body weight


National Cancer Institute


University of Bradford



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.