Nanoparticle-mediated knockdown of DNA repair sensitizes cells to radiotherapy and extends survival in a genetic mouse model of glioblastoma

Forrest M. Kievit, Kui Wang, Tatsuya Ozawa, Aria W. Tarudji, John R. Silber, Eric C. Holland, Richard G. Ellenbogen, Miqin Zhang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Glioblastoma (GBM) remains incurable, and recurrent tumors rarely respond to standard-of-care radiation and chemo-therapies. Therefore, strategies that enhance the effects of these therapies should provide significant benefits to GBM patients. We have developed a nanoparticle delivery vehicle that can stably bind and protect nucleic acids for specific delivery into brain tumor cells. These nanoparticles can deliver therapeutic siRNAs to sensitize GBM cells to radiotherapy and improve GBM treatment via systemic administration. We show that nanoparticle-mediated knockdown of the DNA repair protein apurinic endonuclease 1 (Ape1) sensitizes GBM cells to radiotherapy and extend survival in a genetic mouse model of GBM. Specific knockdown of Ape1 activity by 30% in brain tumor tissue doubled the extended survival achieved with radiotherapy alone. Ape1 is a promising target for increasing the effectiveness of radiotherapy, and nanoparticle-mediated delivery of siRNA is a promising strategy for tumor specific knockdown of Ape1.

Original languageEnglish (US)
Pages (from-to)2131-2139
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume13
Issue number7
DOIs
Publication statusPublished - Oct 2017

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Keywords

  • Ape1/APEX1
  • Glioblastoma
  • Nanoparticle
  • Radiosensitization
  • siRNA

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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