siRNA Nanoparticle Suppresses Drug-Resistant Gene and Prolongs Survival in an Orthotopic Glioblastoma Xenograft Mouse Model

Kui Wang, Forrest M. Kievit, Peter A. Chiarelli, Zachary R. Stephen, Guanyou Lin, John R. Silber, Richard G. Ellenbogen, Miqin Zhang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Temozolomide (TMZ) is the standard-of-care chemotherapy drug for treating glioblastomas (GBMs), the most aggressive cancer that affects people of all ages. However, its therapeutic efficacy is limited by the drug-resistance mediated by a DNA repair protein, O6-methylguanine-DNA methyltransferase (MGMT), which eliminates the TMZ-induced DNA lesions. Here, the development of an iron oxide nanoparticle (NP) system for targeted delivery of small interfering RNAs to suppress the TMZ-resistance gene (MGMT) is reported. The NPs are able to overcome biological barriers, bind specifically to tumor cells, and reduce MGMT expression in tumors of mice bearing orthotopic GBM serially passaged patient-derived xenografts. The treatment with sequential administration of this NP and TMZ result in increased apoptosis of GBM stem-like cells, reduced tumor growth, and significantly prolonged survival as compared to mice treated with TMZ alone. This study introduces an approach that holds great promise to improve the outcomes of GBM patients.

Original languageEnglish (US)
Article number2007166
JournalAdvanced Functional Materials
Volume31
Issue number6
DOIs
StatePublished - Feb 3 2021

Keywords

  • O -methylguanine-DNA methyltransferase
  • brain tumors
  • drug-resistances
  • glioblastoma stem cells
  • nanoparticles
  • small interfering RNA deliveries
  • treatment resistances

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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