Molecular Imaging and Biology

, Volume 16, Issue 5, pp 680–689 | Cite as

Combination Treatment with Theranostic Nanoparticles for Glioblastoma Sensitization to TMZ

  • Byunghee Yoo
  • Marytheresa A. Ifediba
  • Subrata Ghosh
  • Zdravka Medarova
  • Anna MooreEmail author
Research Article



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.


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).


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.


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.

Key words

Theranostic Nanoparticle Glioblastoma multiforme siRNA MRI Chlorotoxin Targeting Temozolomide 



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.

Supplementary material

11307_2014_734_MOESM1_ESM.pdf (1.4 mb)
ESM 1 (PDF 1,433 kb)


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Copyright information

© World Molecular Imaging Society 2014

Authors and Affiliations

  • Byunghee Yoo
    • 1
  • Marytheresa A. Ifediba
    • 1
    • 2
  • Subrata Ghosh
    • 1
  • Zdravka Medarova
    • 1
  • Anna Moore
    • 1
    Email author
  1. 1.Molecular Imaging Laboratory, MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of RadiologyMassachusetts General Hospital/Harvard Medical SchoolCharlestownUSA
  2. 2.Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA

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