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A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival
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| Zeitschriftentitel: | Molecular Cancer Therapeutics |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , |
| In: | Molecular Cancer Therapeutics, 16, 2017, 9, S. 1909-1921 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
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. 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. |
|---|---|
| author |
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. |
| spellingShingle |
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. Molecular Cancer Therapeutics A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival Cancer Research Oncology |
| author_sort |
mohanty, suchismita |
| spelling |
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. 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-17-0022 <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> A Novel Theranostic Strategy for <i>MMP-14</i>–Expressing Glioblastomas Impacts Survival Molecular Cancer Therapeutics |
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| title |
A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_unstemmed |
A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_full |
A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_fullStr |
A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_full_unstemmed |
A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_short |
A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_sort |
a novel theranostic strategy for <i>mmp-14</i>–expressing glioblastomas impacts survival |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1535-7163.mct-17-0022 |
| publishDate |
2017 |
| physical |
1909-1921 |
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<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> |
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| author | 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. |
| author_facet | 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., 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. |
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| description | <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> |
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| spelling | 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. 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-17-0022 <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> A Novel Theranostic Strategy for <i>MMP-14</i>–Expressing Glioblastomas Impacts Survival Molecular Cancer Therapeutics |
| spellingShingle | 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., Molecular Cancer Therapeutics, A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival, Cancer Research, Oncology |
| title | A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_full | A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_fullStr | A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_full_unstemmed | A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_short | A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| title_sort | a novel theranostic strategy for <i>mmp-14</i>–expressing glioblastomas impacts survival |
| title_unstemmed | A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1535-7163.mct-17-0022 |