Titanium nanoparticles
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TiO2 nanoparticles (NPs) are extensively used in various applications, highlighting the importance of ongoing research into their effects. This work belongs among rare whole-body inhalation studies investigating the effects of TiO2 NPs on mice. Unlike previous studies, the concentration of TiO2 NPs in the inhalation chamber (130.8 μg/m3) was significantly lower. This 11-week study on mice confirmed in vivo the presence of TiO2 NPs in lung macrophages and type II pneumocytes including their intracellular localization by using the electron microscopy and the state-of-the-art methods detecting NPs' chemical identity/crystal structure, such as the energy-dispersed X-ray spectroscopy (EDX), cathodoluminescence (CL), and detailed diffraction pattern analysis using powder nanobeam diffraction (PNBD). For the first time in inhalation study in vivo, the alterations in erythrocyte morphology with evidence of echinocytes and stomatocytes, accompanied by iron accumulation in spleen, liver, and kidney, are reported following NP's exposure. Together with the histopathological evidence of hyperaemia in the spleen and kidney, and haemosiderin presence in the spleen, the finding of NPs containing iron might suggest the increased decomposition of damaged erythrocytes. The detection of TiO2 NPs on erythrocytes through CL analysis confirmed their potential systemic availability. On the contrary, TiO2 NPs were not confirmed in other organs (spleen, liver, and kidney); Ti was detected only in the kidney near the detection limit.
- MeSH
- aplikace inhalační MeSH
- erytrocyty * účinky léků patologie MeSH
- inhalační expozice * škodlivé účinky MeSH
- kovové nanočástice * toxicita MeSH
- myši MeSH
- nanočástice * toxicita MeSH
- plíce * účinky léků metabolismus patologie MeSH
- testy subchronické toxicity MeSH
- titan * toxicita farmakokinetika aplikace a dávkování MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: A critical step preceding the potential biomedical application of nanoparticles is the evaluation of their immunomodulatory effects. Such nanoparticles are expected to enter the bloodstream where they can be recognized and processed by circulating monocytes. Despite the required biocompatibility, this interaction can affect intracellular homeostasis and modulate physiological functions, particularly inflammation. This study focuses on titanium dioxide (TiO2) as an example of relatively low cytotoxic nanoparticles with potential biomedical use and aims to evaluate their possible modulatory effects on the inflammasome-based response in human primary monocytes. METHODS: Monocyte viability, phenotypic changes, and cytokine production were determined after exposure to TiO2 (diameter, 25 nm; P25) alone. In the case of the modulatory effects, we focused on NLRP3 activation. The production of IL-1β and IL-10 was evaluated after (a) simultaneous activation of monocytes with bacterial stimuli muramyl dipeptide (MDP), or lipopolysaccharide (LPS), and TiO2 (co-exposure model), (b) prior activation with TiO2 alone and subsequent exposure to bacterial stimuli MDP or LPS. The differentiation of TiO2-treated monocytes into macrophages and their polarization were also assessed. RESULTS: The selected TiO2 concentration range (30-120 μg/mL) did not induce any significant cytotoxic effects. The highest dose of TiO2 promoted monocyte survival and differentiation into macrophages, with the M2 subset being the most prevalent. Nanoparticles alone did not induce substantial production of inflammatory cytokines IL-1β, IL-6, or TNF-α. The immunomodulatory effect on NLRP3 depended on the type of costimulant used. While co-exposure of monocytes to MDP and TiO2 boosted NLRP3 activity, co-exposure to LPS and TiO2 inhibited NLRP3 by enhancing IL-10 release. The inhibitory effect of TiO2 on NLRP3 based on the promotion of IL-10 was confirmed in a post-exposure model for both costimulants. CONCLUSION: This study confirmed a non-negligible modulatory effect on primary monocytes in their inflammasome-based response and differentiation ability.
- MeSH
- acetylmuramyl-alanyl-isoglutamin farmakologie MeSH
- buněčná diferenciace účinky léků MeSH
- cytokiny metabolismus MeSH
- inflamasomy účinky léků MeSH
- interleukin-10 metabolismus MeSH
- interleukin-1beta metabolismus MeSH
- kovové nanočástice chemie toxicita MeSH
- kultivované buňky MeSH
- lidé MeSH
- lipopolysacharidy * farmakologie MeSH
- makrofágy účinky léků MeSH
- monocyty * účinky léků MeSH
- nanočástice chemie toxicita MeSH
- protein NLRP3 * metabolismus MeSH
- titan * chemie farmakologie toxicita MeSH
- viabilita buněk * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Targeted alpha therapy (TAT) is an effective option for cancer treatment. To maximize its efficacy and minimize side effects, carriers must deliver radionuclides to target tissues. Most of the nuclides used in TAT decay via the alpha cascade, producing several radioactive daughter nuclei with sufficient energy to escape from the original carrier. Therefore, studying these daughter atoms is crucial in the search for new carriers. Nanoparticles have potential as carriers due to their structure, which can prevent the escape of daughter atoms and reduce radiation exposure to non-target tissues. This work focuses on determining the released activity of 221Fr and 213Bi resulting from the decay of 225Ac labelled TiO2 nanoparticles. RESULTS: Labelling of TiO2 nanoparticles has shown high sorption rates of 225Ac and its progeny, 221Fr and 213Bi, with over 92 % of activities sorbed on the nanoparticle surface for all measured radionuclides. However, in the quasi-dynamic in vitro system, the released activity of 221Fr and 213Bi is strongly dependent on the nanoparticles concentration, ranging from 15 % for a concentration of 1 mg/mL to approximately 50 % for a nanoparticle concentration of 10 μg/mL in saline solution. The released activities of 213Bi were lower, with a maximum value of around 20 % for concentrations of 0.05, 0.025, and 0.01 mg/mL. The leakage of 225Ac and its progeny was tested in various biological matrices. Minimal released activity was measured in saline at around 10 % after 48 h, while the maximum activity was measured in blood serum and plasma at 20 %. The amount of 225Ac released into the media was minimal (<3 %). The in vitro results were confirmed in a healthy mouse model. The difference in %ID/g was clearly visible immediately after dissection and again after 6 h when 213Bi reached equilibrium with 225Ac. CONCLUSION: The study verified the potential release of 225Ac progeny from the labelled TiO2 nanoparticles. Experiments were performed to determine the dependence of released activity on nanoparticle concentration and the biological environment. The results demonstrated the high stability of the prepared 225Ac@TiO2 NPs and the potential release of progeny over time. In vivo studies confirmed our hypothesis. The data obtained suggest that the daughter atoms can escape from the original carrier and follow their own biological pathways in the organism.
- MeSH
- aktinium * chemie MeSH
- izotopové značení MeSH
- myši MeSH
- nanočástice * chemie MeSH
- radionuklidy chemie MeSH
- titan * chemie MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We analyzed gene expression in THP-1 cells exposed to metal-based nanomaterials (NMs) [TiO2 (NM-100), ZnO (NM-110), SiO2 (NM-200), Ag (NM-300 K)]. A functional enrichment analysis of the significant differentially expressed genes (DEGs) identified the key modulated biological processes and pathways. DEGs were used to construct protein-protein interaction networks. NM-110 and NM-300 K induced changes in the expression of genes involved in oxidative and genotoxic stress, immune response, alterations of cell cycle, detoxification of metal ions and regulation of redox-sensitive pathways. Both NMs shared a number of highly connected protein nodes (hubs) including CXCL8, ATF3, HMOX1, and IL1B. NM-200 induced limited transcriptional changes, mostly related to the immune response; however, several hubs (CXCL8, ATF3) were identical with NM-110 and NM-300 K. No effects of NM-100 were observed. Overall, soluble nanomaterials NM-110 and NM-300 K exerted a wide variety of toxic effects, while insoluble NM-200 induced immunotoxicity; NM-100 caused no detectable changes on the gene expression level.
- MeSH
- hemoxygenasa-1 MeSH
- interleukin-8 metabolismus genetika MeSH
- kovové nanočástice toxicita MeSH
- lidé MeSH
- mapy interakcí proteinů * účinky léků MeSH
- nanostruktury toxicita MeSH
- oxid křemičitý toxicita MeSH
- oxid zinečnatý toxicita chemie MeSH
- stříbro * toxicita MeSH
- THP-1 buňky MeSH
- titan * toxicita MeSH
- transkripční faktor ATF3 genetika metabolismus MeSH
- transkriptom účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Nanoparticles (NPs) have a wide use in various field of industry and in medicine, where they represent a promise for their antimicrobial effects. Simultaneous application of NPs and therapeutic stem cells can speed up tissue regeneration and improve healing process but there is a danger of negative impacts of NPs on stem cells. Therefore, we tested effects of four types of metal antimicrobial NPs on characteristics and function properties of mouse mesenchymal stem cells (MSCs) in vitro. All types of tested NPs, i.e. zinc oxide, silver, copper oxide and titanium dioxide, exerted negative effects on the expression of phenotypic markers, metabolic activity, differentiation potential, expression of genes for immunoregulatory molecules and on production of cytokines and growth factors by MSCs. However, there were apparent differences in the impact of individual types of NPs on tested characteristics and function properties of MSCs. The results showed that individual types of NPs influence the activity of MSCs, and thus the use of metal NPs during tissue regeneration and in combination with stem cell therapy should be well considered.
- MeSH
- antiinfekční látky * MeSH
- buněčná diferenciace MeSH
- hojení ran MeSH
- kovové nanočástice * toxicita MeSH
- mezenchymální kmenové buňky * MeSH
- myši MeSH
- nanočástice * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The emergence of antibiotic resistance in pathogenic bacteria has become a global threat, encouraging the adoption of efficient and effective alternatives to conventional antibiotics and promoting their use as replacements. Titanium dioxide nanoparticles (TiO2 NPs) have been reported to exhibit antibacterial properties. In this study, we synthesized and characterized TiO2 NPs in anatase and rutile forms with surface modification by geraniol (GER). RESULTS: The crystallinity and morphology of modified TiO2 NPs were analyzed by UV/Vis spectrophotometry, X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) with elemental mapping (EDS). The antimicrobial activity of TiO2 NPs with geraniol was assessed against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. The minimum inhibitory concentration (MIC) values of modified NPs ranged from 0.25 to 1.0 mg/ml against all bacterial strains, and the live dead assay and fractional inhibitory concentration (FIC) supported the antibacterial properties of TiO2 NPs with GER. Moreover, TiO2 NPs with GER also showed a significant decrease in the biofilm thickness of MRSA. CONCLUSIONS: Our results suggest that TiO2 NPs with GER offer a promising alternative to antibiotics, particularly for controlling antibiotic-resistant strains. The surface modification of TiO2 NPs by geraniol resulted in enhanced antibacterial properties against multiple bacterial strains, including antibiotic-resistant MRSA. The potential applications of modified TiO2 NPs in the biomedical and environmental fields warrant further investigation.
Hydrogel based matrices and titanium dioxide (TiO2) nanoparticles (NPs) are well established materials in bone tissue engineering. Nevertheless, there is still a challenge to design appropriate composites with enhanced mechanical properties and improved cell growth. Progressing in this direction, we synthesized nanocomposite hydrogels by impregnating TiO2 NPs in a chitosan and cellulose-based hydrogel matrix containing polyvinyl alcohol (PVA), to enhance the mechanical stability and swelling capacity. Although, TiO2 has been incorporated into single and double component matrix systems, it has rarely been combined with a tri-component hydrogel matrix system. The doping of NPs was confirmed by Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and small- and wide-angle X-ray scattering. Our results showed that incorporation of TiO2 NPs improved the tensile properties of the hydrogels significantly. Furthermore, we performed biological evaluation of scaffolds, swelling degree, bioactivity assessment, and hemolytic tests to prove that all types of hydrogels were safe for use in the human body. The culturing of human osteoblast-like cells MG-63 on hydrogels showed better adhesion of cells in the presence of TiO2 and showed increasing proliferation with increasing amount of TiO2. Our results showed that the sample with the highest TiO2 concentration, CS/MC/PVA/TiO2 (1 %) had the best biological properties.
- MeSH
- celulosa farmakologie MeSH
- chitosan * farmakologie chemie MeSH
- hydrogely farmakologie chemie MeSH
- lidé MeSH
- nanočástice * chemie MeSH
- polyvinylalkohol chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Modern micro/nanorobots can perform multiple tasks for biomedical and environmental applications. Particularly, magnetic microrobots can be completely controlled by a rotating magnetic field and their motion powered and controlled without the use of toxic fuels, which makes them most promising for biomedical application. Moreover, they are able to form swarms, allowing them to perform specific tasks at a larger scale than a single microrobot. In this work, they developed magnetic microrobots composed of halloysite nanotubes as backbone and iron oxide (Fe3 O4 ) nanoparticles as magnetic material allowing magnetic propulsion and covered these with polyethylenimine to load ampicillin and prevent the microrobots from disassembling. These microrobots exhibit multimodal motion as single robots as well as in swarms. In addition, they can transform from tumbling to spinning motion and vice-versa, and when in swarm mode they can change their motion from vortex to ribbon and back again. Finally, the vortex motion mode is used to penetrate and disrupt the extracellular matrix of Staphylococcus aureus biofilm colonized on titanium mesh used for bone restoration, which improves the effect of the antibiotic's activity. Such magnetic microrobots for biofilm removal from medical implants could reduce implant rejection and improve patients' well-being.
- MeSH
- biofilmy * MeSH
- fyzikální jevy MeSH
- lidé MeSH
- magnetické pole MeSH
- pohyb těles MeSH
- titan * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Negative impacts of nanomaterials on stem cells and cells of the immune system are one of the main causes of an impaired or slowed tissue healing. Therefore, we tested effects of four selected types of metal nanoparticles (NPs): zinc oxide (ZnO), copper oxide (CuO), silver (Ag), and titanium dioxide (TiO2) on the metabolic activity and secretory potential of mouse mesenchymal stem cells (MSCs), and on the ability of MSCs to stimulate production of cytokines and growth factors by macrophages. Individual types of nanoparticles differed in the ability to inhibit metabolic activity, and significantly decreased the production of cytokines and growth factors (interleukin-6, vascular endothelial growth factor, hepatocyte growth factor, insulin-like growth factor-1) by MSCs, with the strongest inhibitory effect of CuO NPs and the least effect of TiO2 NPs. The recent studies indicate that immunomodulatory and therapeutic effects of transplanted MSCs are mediated by macrophages engulfing apoptotic MSCs. We co-cultivated macrophages with heat-inactivated MSCs which were untreated or were preincubated with the highest nontoxic concentrations of metal NPs, and the secretory activity of macrophages was determined. Macrophages cultivated in the presence of both untreated MSCs or MSCs preincubated with NPs produced significantly enhanced and comparable levels of various cytokines and growth factors. These results suggest that metal nanoparticles inhibit therapeutic properties of MSCs by a direct negative effect on their secretory activity, but MSCs cultivated in the presence of metal NPs have preserved the ability to stimulate cytokine and growth factor production by macrophages.
Titanium dioxide nanoparticles (TiO2 NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on potential harmful effects of TiO2 NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO2 NPs (0.00167 and 0.1308 mg TiO2/m3) in mice. A dose-dependent effect of TiO2 NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO2 NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO2 NP exposure.
- Publikační typ
- časopisecké články MeSH
