Nanoparticles of silver and titanium can increase temozolomide sensitivity against human glioblastoma: an in vitro study on apoptosis and inflammation.

Temozolomide (TMZ) is one of the alkylating drugs that are preferably employed to treat human glioblastoma (GBM). However, its immune escape and resistance by GBM limit the survival of patients. The present in vitro study was undertaken to investigate whether AgNPs or TiONPs can enhance the sensitivity of GBM to TMZ through apoptotic and/or inflammatory responses. Human glioblastoma U87MG cells were exposed to different concentrations of TMZ, AgNPs, and TiONPs after determining respective IC values for 24 h at 37 °C under a 5% CO atmosphere. Thereafter, biomarkers of LPO (malondialdehyde), apoptosis (caspase 3, 9), inflammation (TNF-α and IL-12), and DNA fragmentation (CAD) were assayed. Acridine orange/ethidium bromide staining of GBM was also performed. Combined treatments of GBM with TMZ and AgNPs or TiONPs showed a mild stimulatory effect on selected biomarkers of LPO (MDA), apoptosis (caspase3, 9), DNA fragmentation (CAD), and inflammatory cytokines (TNF-α and IL-12) in comparison to those GBM cells treated with TMZ alone. Microscopical results on apoptosis supported these results. It is suggested that overexpression of drug efflux transporters, increased apoptosis, inflammation, and drug delivery directly to cells might have contributed to enhanced protective effects of TMZ, in combination with nanoparticles.