Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles.
ABSTRACT: Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated. Therefore, we determined the sub-toxic effect of three different TiO2 nanoparticles (rutile, anatase and commercially available P25 TiO2 nanoparticles) on primary rat cortical astrocytes. We evaluated some events related to astrocyte functions and mitochondrial dysregulation: (1) glutamate uptake; (2) redox signaling mechanisms by measuring ROS production; (3) the expression patterns of dynamin-related proteins (DRPs) and mitofusins 1 and 2, whose expression is central to mitochondrial dynamics; and (4) mitochondrial morphology by MitoTracker® Red CMXRos staining. Anatase, rutile and P25 were found to have LC50 values of 88.22 ± 10.56 ppm, 136.0 ± 31.73 ppm and 62.37 ± 9.06 ppm respectively indicating nanoparticle specific toxicity. All three TiO2 nanoparticles induced a significant loss in glutamate uptake indicative of a loss in vital astrocyte function. TiO2 nanoparticles also induced an increase in reactive oxygen species generation, and a decrease in mitochondrial membrane potential, suggesting mitochondrial damage. TiO2 nanoparticle exposure altered expression patterns of DRPs at low concentrations (25 ppm) and apoptotic fission at high concentrations (100 ppm). TiO2 nanoparticle exposure also resulted in changes to mitochondrial morphology confirmed by mitochondrial staining. Collectively, our data provide compelling evidence that TiO2 nanoparticle exposure has potential implications in astrocyte-mediated neurological dysfunction.
Project description:Titanium dioxide (TiO2) nanoparticles are one of the most highly manufactured and employed nanomaterials in the world with applications in copious industrial and consumer products. The liver is a major accumulation site for many nanoparticles, including TiO2, directly through intentional exposure or indirectly through unintentional ingestion via water, food or animals and increased environmental contamination. Growing concerns over the current usage of TiO2 coupled with the lack of mechanistic understanding of its potential health risk is the motivation for this study. Here we determined the toxic effect of three different TiO2 nanoparticles (commercially available rutile, anatase and P25) on primary rat hepatocytes. Specifically, we evaluated events related to hepatocyte functions and mitochondrial dynamics: (1) urea and albumin synthesis using colorimetric and ELISA assays, respectively; (2) redox signaling mechanisms by measuring reactive oxygen species (ROS) production, manganese superoxide dismutase (MnSOD) activity and mitochondrial membrane potential (MMP); (3) OPA1 and Mfn-1 expression that mediates the mitochondrial dynamics by PCR; and (4) mitochondrial morphology by MitoTracker Green FM staining. All three TiO2 nanoparticles induced a significant loss (p < 0.05) in hepatocyte functions even at concentrations as low as 50 ppm with commercially used P25 causing maximum damage. TiO2 nanoparticles induced a strong oxidative stress in primary hepatocytes. TiO2 nanoparticles exposure also resulted in morphological changes in mitochondria and substantial loss in the fusion process, thus impairing the mitochondrial dynamics. Although this study demonstrated that TiO2 nanoparticles exposure resulted in substantial damage to primary hepatocytes, more in vitro and in vivo studies are required to determine the complete toxicological mechanism in primary hepatocytes and subsequently liver function.
Project description:Currently, Degussa P25, with the typical mixed phases of anatase and rutile TiO2, is widely applied as the commercial photocatalysts. However, there are still some of obstacles for the P25 nanoparticles with totally high photocatalytic activities, especially for the catalytic stability due to their inevitable aggregation of the nanoparticles when used as the photocatalysts. In the present work, we reported the exploration of a novel TiO2 photocatalyst, which could offer an ideal platform for synergetic combination of the mixed-phase composition, hollow architecture and mesoporous walls for the desired excellent photocatalytic efficiency and robust stability. The mesoporous TiO2 hollow nanofibers were fabricated via a facile single capillary electrospinning technique, in which the foaming agents were used for creating mesopores throughout the walls of the hollow fibers. The obtained hollow fibers exhibit a high purity and possess the mixed phases of 94.6% anatase and 5.4% rutile TiO2. As compared to P25, the as-fabricated mesoporous TiO2 hollow fibers exhibited much higher efficient photocatalytic activities and stabilities toward the hydrogen evolution with a rate of ~499.1??mol g(-1)·h(-1) and ~99.5% degradation Rhodamine B (RhB) in 60?min, suggesting their promising application in efficient photocatalysts.
Project description:As a benchmark photocatalyst, commercial P25-TiO2 has been widely used for various photocatalytic applications. However, the low surface area and poorly porous structure greatly limit its performance. Herein, uniform ordered mesoporous TiO2 microspheres (denoted as Meso-TiO2-X; X represents the rutile percentage in the resultant microspheres) with controllable anatase/rutile phase junctions and radially oriented mesochannels are synthesized by a coordination-mediated self-assembly approach. The anatase/rutile ratio in the resultant microspheres can be facilely adjusted as desired (rutile percentage: 0-100) by changing the concentration of hydrochloric acid. As a typical one, the as-prepared Meso-TiO2-25 microspheres have a similar anatase/rutile ratio to commercial P25. But the surface area (78.6 m2 g-1) and pore volume (0.39 cm3 g-1) of the resultant microspheres are larger than those of commercial P25. When used as the photocatalyst for H2 generation, the Meso-TiO2-25 delivers high solar-driven H2 evolution rates under air mass 1.5 global (AM 1.5 G) and visible-light (λ > 400 nm), respectively, which are significantly larger than those of commercial P25. This coordination-mediated self-assembly method paves a new way toward the design and synthesis of high performance mesoporous photocatalysts.
Project description:Engineered nanomaterials (ENMs) have potential benefits, but they also present safety concerns for human health. Interlaboratory studies in rodents using standardized protocols are needed to assess ENM toxicity.Four laboratories evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA), and three labs evaluated Sprague-Dawley (SD) or Fisher 344 (F344) rats following intratracheal instillation (IT). ENMs tested included three forms of titanium dioxide (TiO2) [anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NBs)] and three forms of multiwalled carbon nanotubes (MWCNTs) [original (O), purified (P), and carboxylic acid "functionalized" (F)]. One day after treatment, bronchoalveolar lavage fluid was collected to determine differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2 forms) and 21 days (MWCNTs) after treatment.TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in three of four labs. TiO2-NB caused neutrophilia in rats at 1 day in two of three labs, and TiO2-P25 and TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in three of four mouse labs and in all rat labs. Three of four labs observed similar histopathology to O-MWCNTs and TiO2-NBs in mice.ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although interlaboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these interlaboratory comparisons.
Project description:In this article, we demonstrate the position-controlled hydrothermal growth of rutile TiO2 nanorods using a new scanning probe lithography method in which a silicon tip, commonly used for atomic force microscopy, was pulled across an anatase TiO2 film. This process scratches the film causing tiny anatase TiO2 nanoparticles to form on the surface. According to previous reports, these anatase particles convert into rutile nanocrystals and provide the growth of rutile TiO2 nanorods in well-defined areas. Due to the small tip radius, the resolution of this method is excellent and the method is quite inexpensive compared to electron-beam lithography and similar methods providing a position-controlled growth of semiconducting TiO2 nanostructures.
Project description:Titanium dioxide (TiO2) nanoparticles are commonly found in consumer products, such as sunscreens, and human dermal exposures are relatively high. Research suggests potential differences in the toxicity of anatase and rutile crystalline forms of TiO2. Additionally, transition metal dopants are frequently used to enhance physicochemical properties of TiO2, and the toxicity of these nanoparticles are not extensively studied. Therefore, this work examined the keratinocyte toxicity and in vivo skin allergy responses after treatment with 30 nm anatase, 30 nm rutile, or <100 nm Mn-doped TiO2 nanoparticles. After a 24-hour exposure, there were no differences in keratinocyte cytotoxicity; however, Mn-doped TiO2 nanoparticles induced significant in vitro ROS generation and in vivo skin swelling responses in a model of allergic contact dermatitis.
Project description:Emerging nanomaterials are being manufactured with varying particle sizes, morphologies, and crystal structures in the pursuit of achieving outstanding functional properties. These variations in these key material properties of nanoparticles may affect their environmental fate and transport. To date, few studies have investigated this important aspect of nanoparticles' environmental behavior. In this study, the aggregation kinetics of ten different TiO2 nanoparticles (5 anatase and 5 rutile each with varying size) was systematically evaluated. Our results show that, as particle size increases, the surface charge of both anatase and rutile TiO2 nanoparticles shifts toward a more negative value, and, accordingly, the point of zero charge shifts toward a lower value. The colloidal stability of anatase sphere samples agreed well with DLVO theoretical predictions, where an increase in particle size led to a higher energy barrier and therefore greater critical coagulation concentration. In contrast, the critical coagulation concentration of rutile rod samples correlated positively with the specific surface area, i.e., samples with higher specific surface area exhibited higher stability. Finally, due to the large innate negative surface charge of all the TiO2 samples at the pH value (pH = 8) tested, the addition of natural organic matter was observed to have minimal effect on TiO2 aggregation kinetics, except for the smallest rutile rods that showed decreased stability in the presence of natural organic matter.
Project description:TiO2 nanoparticles were synthesized from titanium isopropoxide by a simple peptization method using sulfuric, nitric, and acetic acids. The effect of peptizing acid on physicochemical and photocatalytic properties of TiO2 powders was studied. The structural properties of synthesized TiO2 powders were analyzed by using XRD, TEM, N2-physisorption, Raman, DR UV-vis, FTIR, and X-ray photoelectron spectroscopy techniques. The characterization results showed that acetic acid peptization facilitated the formation of pure anatase phase after thermal treatment at 500 °C; in contrast, nitric acid peptization led to a major rutile phase formation (67%). Interestingly, the sample peptized using sulfuric acid yielded 95% anatase and 5% rutile phases. The photocatalytic activity of synthesized TiO2 nanoparticles was evaluated for degradation of selected organic dyes (crystal violet, methylene blue, and p-nitrophenol) in aqueous solution. The results confirmed that the TiO2 sample peptized using nitric acid (with rutile and anatase phases in 3:1 ratio) offered the highest activity for degradation of organic dyes, although, TiO2 samples peptized using sulfuric acid and acetic acid possessed smaller particle size, higher band gap energy, and high surface area. Interestingly, TiO2 sample peptized with nitric acid possessed relatively high theoretical photocurrent density (0.545 mAcm-2) and pore diameter (150 Å), which are responsible for high electron-hole separation efficiency and diffusion and mass transportation of organic reactants during the photochemical degradation process. The superior activity of TiO2 sample peptized with nitric acid is due to the effective transfer of photogenerated electrons between rutile and anatase phases.
Project description:Herein, we have fabricated rutile TiO2 nanorod-coupled ?-Fe2O3 by a wet-chemical process. It is demonstrated that the visible activities for photoelectrochemical water oxidation and for degrading pollutant of ?-Fe2O3 are greatly enhanced after coupling a proper amount of rutile nanorods. The enhanced activity is attributed to the prolonged lifetime and improved separation of photogenerated charges mainly by the transient surface photovoltage responses. Interestingly, the observed EPR signals (with g? = 1.963 and g|| = 1.948) of Ti(3+) in the fabricated TiO2-Fe2O3 nanocomposite at ultra low temperature (1.8?k) after visible laser excitation, along with the electrochemical impedance spectra and the normalized photocurrent action spectra, testify evidently that the spacial transfers of visible-excited high-energy electrons of ?-Fe2O3 to TiO2 could happen. Moreover, it is confirmed that it is more favorable for the uncommon electron transfers of ?-Fe2O3 to rutile than to anatase. This is responsible for the much obvious enhancement of visible activity of Fe2O3 after coupling with rutile TiO2, compared with anatase and phase-mixed P25 ones. This work would help us to deeply understand the uncommon photophysical processes, and also provide a feasible route to improve the photocatalytic performance of visible-response semiconductor photocatalyst for water splitting and pollutant degradation.
Project description:Using a simple hydrothermal synthesis, the crystal structure of TiO2 nanoparticles was controlled from rutile to anatase using a sugar alcohol, D-sorbitol. Adding small amounts of D-sorbitol to an aqueous TiCl4 solution resulted in changes in the crystal phase, particle size, and surface area by affecting the hydrolysis rate of TiCl4. These changes led to improvements of the solar-to-electrical power conversion efficiency (?) of dye-sensitized solar cells (DSSC) fabricated using these nanoparticles. A postulated reaction mechanism concerning the role of D-sorbitol in the formation of rutile and anatase was proposed. Fourier-transform infrared spectroscopy, (13)C NMR spectroscopy, and dynamic light scattering analyses were used to better understand the interaction between the Ti precursor and D-sorbitol. The crystal phase and size of the synthesized TiO2 nanocrystallites as well as photovoltaic performance of the DSSC were examined using X-ray diffraction, Raman spectroscopy, field-emission scanning electron microscopy, high-resolution transmission electron microscopy, and photocurrent density-applied voltage spectroscopy measurement techniques. The DSSC fabricated using the anatase TiO2 nanoparticles synthesized in the presence of D-sorbitol, exhibited an enhanced ? (6%, 1.5-fold improvement) compared with the device fabricated using the rutile TiO2 synthesized without D-sorbitol.