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 language | English (US) |
---|---|
Pages (from-to) | 337-345 |
Number of pages | 9 |
Journal | Journal of Bionanoscience |
Volume | 11 |
Issue number | 5 |
DOIs | |
State | Published - Oct 2017 |
Externally published | Yes |
Keywords
- Epigenetics
- Glioblastoma multiforme
- Hypoxia
- Oxygen nanobubbles
- Temozolomide
ASJC Scopus subject areas
- Biotechnology
- Biomaterials
- Biomedical Engineering