Effects of Titanium Dioxide Nanoparticle Aggregate Size on Gene Expression

Titanium dioxide (titania) nanoparticle aggregation is an important factor in understanding cytotoxicity. However, the effect of the aggregate size of nanoparticles on cells is unclear. We prepared two sizes of titania aggregate particles and investigated their biological activity by analyzing biomarker expression based on mRNA expression analysis. The aggregate particle sizes of small and large aggregated titania were 166 nm (PDI = 0.291) and 596 nm (PDI = 0.417), respectively. These two size groups were separated by centrifugation from the same initial nanoparticle sample. We analyzed the gene expression of biomarkers focused on stress, inflammation, and cytotoxicity. Large titania aggregates show a larger effect on cell viability and gene expression when compared with the small aggregates. This suggests that particle aggregate size is related to cellular effects

Effect of Polyethylene Glycol Modification of TiO2 Nanoparticles on Cytotoxicity and Gene Expressions in Human Cell Lines

Nanoparticles (NPs) are tiny materials used in a wide range of industrial and medical applications. Titanium dioxide (TiO2) is a type of nanoparticle that is widely used in paints, pigments, and cosmetics; however, little is known about the impact of TiO2 on human health and the environment. Therefore, considerable research has focused on characterizing the potential toxicity of nanoparticles such as TiO2 and on understanding the mechanism of TiO2 NP-induced nanotoxicity through the evaluation of biomarkers. Uncoated TiO2 NPs tend to aggregate in aqueous media, and these aggregates decrease cell viability and induce expression of stress-related genes, such as those encoding interleukin-6 (IL-6) and heat shock protein 70B’ (HSP70B’), indicating that TiO2 NPs induce inflammatory and heat shock responses. In order to reduce their toxicity, we conjugated TiO2 NPs with polyethylene glycol (PEG) to eliminate aggregation. Our findings indicate that modifying TiO2 NPs with PEG reduces their cytotoxicity and reduces the induction of stress-related genes. Our results also suggest that TiO2 NP-induced effects on cytotoxicity and gene expression vary depending upon the cell type and surface modification

Sonodynamic therapy using water-dispersed TiO2-polyethylene glycol compound on glioma cells : Comparison of cytotoxic mechanism with photodynamic therapy

Sonodynamic therapy is expected to be a novel therapeutic strategy for malignant gliomas. The titanium dioxide (TiO2) nanoparticle, a photosensitizer, can be activated by ultrasound. In this study, by using water-dispersed TiO2 nanoparticles, an in vitro comparison was made between the photodynamic and sonodynamic damages on U251 human glioblastoma cell lines. Water-dispersed TiO2 nanoparticles were constructed by the adsorption of chemically modified polyethylene glycole (PEG) on the TiO2 surface (TiO2/PEG). To evaluate cytotoxicity, U251 monolayer cells were incubated in culture medium including 100 μg/ml of TiO2/PEG for three hours and subsequently irradiated by ultraviolet light (5.0 mW/cm2) or 1.0 MHz ultrasound (1.0 W/cm2). Cell survival was estimated by MTT assay 24 hours after irradiation. In the presence of TiO2/PEG, the photodynamic cytotoxic effect was not observed after 20 minutes of an ultraviolet light exposure, while the sonodynamic cytotoxicity effect was almost proportional to the time of sonication. In addition, photodynamic cytotoxicity of TiO2/PEG was almost completely inhibited by radical scavenger, while suppression of the sonodynamic cytotoxic effect was not significant. Results of various fluorescent stains showed that ultrasound-treated cells lost their viability immediately after irradiation, and cell membranes were especially damaged in comparison with ultraviolet-treated cells. These findings showed a potential application of TiO2/PEG to sonodynamic therapy as a new treatment of malignant gliomas and suggested that the mechanism of TiO2/PEG mediated sonodynamic cytotoxicity differs from that of photodynamic cytotoxicity

Development of Sensor Cells Using NF-κB Pathway Activation for Detection of Nanoparticle-Induced Inflammation

The increasing use of nanomaterials in consumer and industrial products has aroused concerns regarding their fate in biological systems. An effective detection method to evaluate the safety of bio-nanomaterials is therefore very important. Titanium dioxide (TiO2), which is manufactured worldwide in large quantities for use in a wide range of applications, including pigment and cosmetic manufacturing, was once thought to be an inert material, but recently, more and more studies have indicated that TiO2 nanoparticles (TiO2 NPs) can cause inflammation and be harmful to humans by causing lung and brain problems. In order to evaluate the safety of TiO2 NPs for the environment and for humans, sensor cells for inflammation detection were developed, and these were transfected with the Toll-like receptor 4 (TLR4) gene and Nuclear Factor Kappa B (NF-κB) reporter gene. NF-κB as a primary cause of inflammation has received a lot of attention, and it can be activated by a wide variety of external stimuli. Our data show that TiO2 NPs-induced inflammation can be detected by our sensor cells through NF-κB pathway activation. This may lead to our sensor cells being used for bio-nanomaterial safety evaluation

Sonodynamic therapy using water-dispersed TiO2-polyethylene glycol compound on glioma cells: Comparison of cytotoxic mechanism with photodynamic therapy

Sonodynamic therapy is expected to be a novel therapeutic strategy for malignant gliomas. The titanium dioxide (TiO2) nanoparticle, a photosensitizer, can be activated by ultrasound. In this study, by using water-dispersed TiO2 nanoparticles, an in vitro comparison was made between the photodynamic and sonodynamic damages on U251 human glioblastoma cell lines. Water-dispersed TiO2 nanoparticles were constructed by the adsorption of chemically modified polyethylene glycole (PEG) on the TiO2 surface (TiO2/PEG). To evaluate cytotoxicity, U251 monolayer cells were incubated in culture medium including 100 μg/ml of TiO2/PEG for three hours and subsequently irradiated by ultraviolet light (5.0 mW/cm2) or 1.0 MHz ultrasound (1.0 W/cm2). Cell survival was estimated by MTT assay 24 hours after irradiation. In the presence of TiO2/PEG, the photodynamic cytotoxic effect was not observed after 20 minutes of an ultraviolet light exposure, while the sonodynamic cytotoxicity effect was almost proportional to the time of sonication. In addition, photodynamic cytotoxicity of TiO2/PEG was almost completely inhibited by radical scavenger, while suppression of the sonodynamic cytotoxic effect was not significant. Results of various fluorescent stains showed that ultrasound-treated cells lost their viability immediately after irradiation, and cell membranes were especially damaged in comparison with ultraviolet-treated cells. These findings showed a potential application of TiO2/PEG to sonodynamic therapy as a new treatment of malignant gliomas and suggested that the mechanism of TiO2/PEG mediated sonodynamic cytotoxicity differs from that of photodynamic cytotoxicity