Yes / 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. / 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
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/12440 |
| Date | 28 June 2017 |
| Creators | Mohanty, S., Chen, Z., Li, K., Ribeiro Morais, Goreti, Klockow, J., Yerneni, K., Pasani, L., Chin, F.T., Mitra, S., Cheshier, S., Chang, E., Gambhir, S.S., Rao, J., Loadman, Paul, Falconer, Robert A., Daldrup-Link, H.E. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| Rights | © 2017 American Association for Cancer Research. Reproduced in accordance with the publisher's self-archiving policy., Unspecified |
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