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<p>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 TiO<sub>2</sub>NPs 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 TiO<sub>2</sub>NPs after determining respective IC<sub>50</sub> values for 24&#xa0;h at 37&#xa0;°C under a 5% CO<sub>2</sub> 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 TiO<sub>2</sub>NPs 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年6月26日

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  • Sakshi Goswami,
  • Yeshvandra Verma,
  • S. V. S. Rana

摘要

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 TiO2NPs 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 TiO2NPs after determining respective IC50 values for 24 h at 37 °C under a 5% CO2 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 TiO2NPs 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.