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Combination Treatment with Theranostic Nanoparticles for Glioblastoma Sensitization to TMZ

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Abstract

Purpose

Tumor resistance to chemotherapeutic drugs is one of the major obstacles in the treatment of glioblastoma multiforme (GBM). In this study, we attempted to modulate tumor response to chemotherapy by combination treatment that included experimental (small interference RNA (siRNA), chlorotoxin) and conventional (temozolomide, TMZ) therapeutics.

Procedures

siRNA therapy was used to silence O6-methylguanine methyltransferase (MGMT), a key factor in brain tumor resistance to TMZ. For targeting of tumor cells, we used chlorotoxin (CTX), a peptide with antitumoral properties. siRNA and CTX were conjugated to iron oxide nanoparticles (NP) that served as the drug carrier and allowed the means to monitor the changes in tumor volume by magnetic resonance imaging (MRI).

Results

Theranostic nanoparticles (termed CTX-NP-siMGMT) were internalized by T98G glioblastoma cells in vitro leading to enhancement of TMZ toxicity. Combination treatment of mice bearing orthotopic tumors with CTX-NP-siMGMT and TMZ led to significant retardation of tumor growth, which was monitored by MRI.

Conclusions

While our results demonstrate that siRNA delivery by targeted nanoparticles resulted in modulating tumor response to chemotherapy in GBM, they also point to a significant contribution of CTX to tumor cell death.

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Acknowledgments

This work was supported in part by T32CA009502 (PI Anna Moore).

Conflict of Interest Statement

Authors declare no potential conflicts of interest relevant to this publication.

Author information

Author notes

  1. Marytheresa A. Ifediba

    Present address: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA

Authors and Affiliations

  1. Molecular Imaging Laboratory, MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Building 75, 13th Street, Charlestown, MA, 02129, USA

    Byunghee Yoo, Marytheresa A. Ifediba, Subrata Ghosh, Zdravka Medarova & Anna Moore

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  1. Byunghee Yoo
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  2. Marytheresa A. Ifediba
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  5. Anna Moore
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Corresponding author

Correspondence to Anna Moore.

Additional information

Byunghee Yoo and Marytheresa A. Ifediba contributed equally to this work.

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Yoo, B., Ifediba, M.A., Ghosh, S. et al. Combination Treatment with Theranostic Nanoparticles for Glioblastoma Sensitization to TMZ. Mol Imaging Biol 16, 680–689 (2014). https://doi.org/10.1007/s11307-014-0734-3

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