Hypoxia re-programming oxygen nanobubbles sensitize human glioblastoma cells to temozolomide via methylation alterations

Pushpak Bhandari, Ouyang Lei, Joseph Irudayaraj

Research output: Contribution to journalArticle

Abstract

Temozolomide (TMZ) treatment leads to antiangiogenesis and chemotherapeutic resistance in glioblastoma multiforme (GBM) by triggering hypoxia-adaptive pathways in the tumor microenvironment. There is a need for enhancing the effectiveness of TMZ treatment while reducing the cytotoxicity caused by the alkylating therapy. Here, we show that perturbation of the methylation levels and hypoxia-adaptive pathways in SF767 GBM cell lines using oxygen nanobubbles (NB) can significantly improve the effectiveness of TMZ treatment. We found that oxygen nanobubbles had a significant effect in increasing cell death and 5 mC methylation levels. Further, nanobubbles were found to localize intracellularly without any assistance from intracellular uptake ligands, indicating the potential of NB as an adjuvant to chemotherapeutics. A 30% increase in efficacy can be obtained using NB as an adjuvant to TMZ with the required TMZ dose. Thus, our elegant approach to utilize NB as a hypoxia and epigenetic pre-conditioning agent is expected to have a significant impact in glioblastoma therapy.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalJournal of Bionanoscience
Volume11
Issue number5
DOIs
StatePublished - Oct 2017
Externally publishedYes

Keywords

  • Epigenetics
  • Glioblastoma multiforme
  • Hypoxia
  • Oxygen nanobubbles
  • Temozolomide

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biomedical Engineering

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