A Novel Approach to Evaluate Titanium Dioxide Nanoparticle–Protein Interaction Through Docking: An Insight into Mechanism of Action (original) (raw)
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Molecular docking of nanosized titanium dioxide material to the extracellular part of GABAB-receptor
Studia Biologica, 2016
A spatial model of nanosized titanium dioxide material was created using Discovery Studio Visualizer software, versions 2.0 and 2.5. A search for and analysis of possible sites of its docking to the extracellular part of GABA B1а receptor subunit were performed using the algorythm for molecular docking PatchDock. The dimensions of the obtained ТіО 2 nanoparticle surface were (18.925 × 3.785 × 19.028) Å. Four potentially possible sites of ТіО 2 docking to the extracellular part of GABA B1а receptor subunit of GABA B were identified. The ТіО 2 nanoparticle demonstrated high affinity of docking to one of the receptor sites with the geometric shape complementarity score of 12562, taking the following values in other sites: 10746; 10370; 10204. The approximate interface area of complex of the extracellular part of GABA B1а receptor subunit of GABA B with ТіО 2 for the site with the highest geometric shape complementarity score was 1949.80 Å, and for others-1273.20 Å, 1261.10 Å and 1170.30 Å, respectively. The evaluation of аtomic contact energy demonstrated the following values for the sites of ТіО 2 nanoparticle docking: 362.92; 173.93; 340.63 and 224.61. The nature of connections, stabilizing the sites of ТіО 2 docking to the extracellular part of GABA B1а receptor subunit of GABA B , was analyzed in accordance to their amino acid composition.
Binding of titanium dioxide nanoparticles to lactate dehydrogenase
Environmental Health and Preventive Medicine, 2011
Objective Measurement of released lactate dehydrogenase (LDH) activity, a commonly used marker of lethal cell injury in both in vitro and in vivo screenings, has been used to assess the cytotoxicity of nanoparticles (NPs), chemical compounds, and environmental factors. We have recently demonstrated that titanium dioxide (TiO 2) particles bind to several serum proteins. In the present study we investigated the binding of TiO 2 NPs to LDH. Methods Purified LDH was incubated with TiO 2 NPs at 37°C for 1 h. The particles were then sedimented by centrifugation, and the activity and quantity of LDH in the supernatant and precipitated fraction were analyzed. Results Incubation with TiO 2 reduced the LDH activity in the supernatant in a dose-dependent manner, while LDH activity in the precipitated fraction increased in a dosedependent manner. Moreover, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed a TiO 2 dose-dependent reduction in the quantity of LDH protein in the supernatant and an increase of LDH in particulate re-suspensions. Conclusions These findings, although based on a purified form of LDH, suggest that TiO 2 NPs bind to LDH, and consequently, TiO 2 NP-induced toxicity could be underestimated by the LDH activity assay.
Formation of potential titanium antigens based on protein binding to titanium dioxide nanoparticles
2008
Degradation products of titanium implants include free ions, organo-metallic complexes, and particles, ranging from nano to macro sizes. The biological effects, especially of nanoparticles, is yet unknown. The main objective of this study was to develop Ti-protein antigens in physiological solutions that can be used in testing of cellular responses. For this purpose, 0.1% TiO 2 nanoparticles less than 100 nm were mixed with human serum albumin (HSA), 0.1% and 1%, in cell culture medium (DMEM, pH 7.2). The Ti concentrations in the resulting solutions were analyzed by inductively coupled plasma mass spectrometry. The stability of the nanoparticles in suspension was analyzed by UV-vis spectrophotometer and Dynamic Light Scattering. The concentration of Ti in suspension was dependent on the presence and concentration of HSA. Albumin prevented high aggregation rate of TiO 2 nanoparticles in cell culture medium. It is shown that nano TiO 2-protein stable aggregates can be produced under physiological conditions at high concentrations, and are candidates for use in cellular tests.
Journal of Nanoparticle Research, 2017
In the past decade, a variety of drug carriers based on mesoporous silica nanoparticles has been extensively reported. However, their biocompatibility still remains debatable, which motivated us to explore the porous nanostructures of other metal oxides, for example titanium dioxide (TiO 2), as potential drug delivery vehicles. Herein, we report the in vitro hemolysis, cytotoxicity, and protein binding of TiO 2 nanoparticles, synthesized by a sol-gel method. The surface of the TiO 2 nanoparticles was modified with hydroxyl, amine, or thiol containing moieties to examine the influence of surface functional groups on the toxicity and protein binding aspects of the nanoparticles. Our study revealed the superior hemocompatibility of pristine, as well as functionalized TiO 2 nanoparticles, compared to that of mesoporous silica, the present gold standard. Among the functional groups studied, aminosilane moieties on the TiO 2 surface substantially reduced the degree of hemolysis (down to 5%). Further, cytotoxicity studies by MTT assay suggested that surface functional moieties play a crucial role in determining the biocompatibility of the nanoparticles. The presence of NH 2functional groups on the TiO 2 nanoparticle surface enhanced the cell viability by almost 28% as compared to its native counterpart (at 100 μg/ml), which was in agreement with the hemolysis assay. Finally, nonspecific protein adsorption on functionalized TiO 2 surfaces was examined using human serum albumin and it was found that negatively charged surface moieties, like-OH and-SH, could mitigate protein adsorption to a significant extent.
Study of the interaction between proteins and TiO2 NPs : nature of the interfacial processes
2015
The extensive use of NPs in a biological environment raises the problem of their assimilation or their toxicity, the main objective of this work is to study the interaction of TiO2 NPs with proteins as well as their possible impact on the structural properties of proteins. Three proteins were chosen, a protein of the extracellular matrix, the collagen, and two proteins of the plasma blood, the albumin and the fibrinogen for their biological importance as well as for their various tridimensional structures. The study of the protein-nanoparticle interaction was realized in solution and in the adsorbed phase under various condition of temperature and incubation time. First, titanium dioxide NPs were synthesized by a solvothermal method, NPs with controlled size and form were obtained. Two types of NPs were selected in order to study the effect of shape and size on the protein-NPs interaction: nano-spheres with a diameter of 8 to 10 nm and nano-rods with a width about 8 nm and a length ...
Toxicology in vitro : an international journal published in association with BIBRA, 2016
The health risks of nanoparticles remain a serious concern given their prevalence from industrial and domestic use. The primary route of titanium dioxide nanoparticle exposure is inhalation. The extent to which nanoparticles contribute to cellular toxicity is known to associate induction of oxidative stress. To investigate this problem further, the effect of titanium dioxide nanoparticles was examined on cell lines representative of alveolo-capillary barrier. The present study showed that all nanoparticle-exposed cell lines displayed ROS generation. Macrophage-like THP-1 and HPMEC-ST1.6R microvascular cells were sensitive to endogenous redox changes and underwent apoptosis, but not alveolar epithelial A549 cells. Genotoxic potential of titanium dioxide nanoparticles was investigated using the activation of γH2AX, activation of DNA repair proteins and cell cycle arrest. In the sensitive cell lines, DNA damage was persistent and activation of DNA repair pathways was observed. Moreover...
Nano Titanium Exposure Induces Cytotoxicity and Oxidative Stress in Human Lung Cells
2017
The titanium dioxide nanoparticles (TNP) are widely using in skin care, biosensing and many other commercial applications. TNP, 82% anatase / 18% rutile, with primary average diameter of 22 ± 6 nm (TNP 20), 87 ± 16 nm (TNP100). So TNP 20 and TNP 100 cell-particle interactions with human cells and human exposure risk are gaining much importance due to their extensive pharmaceutical and nanobased applications. The potential high-risk exposure for TNP generally inhalation route was the most considered. So, the present study investigates the in vitro cytotoxicity and oxidative stress upon exposure to human lung epithelial cells (A549) using 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT). The oxidative stress bioindicators like lactate dehydrogenase (LDH) leakage, glutathione (GSH), lipid peroxidation (TBARS) levels were estimated. Both the TNP 20 and TNP 100 were decreased the cell viability and caused cell membrane damage via increased LDH in A549 cells for 48 h...
Pteridines, 2012
Titanium is extensively used for a wide range of implanted medical devices due to its advantageous combination of physico-chemical and biological properties. Nano-size titanium dioxide (TiO2) is also used in a variety of consumer products. Such widespread use and its potential entry through various routes of the body suggest that TiO2 could pose an exposure risk to humans. Nano-size particles (NP) enter systemic circulation, accumulate and damage tissues that are especially sensitive to oxidative stress. We hypothesized that TiO2 NPs can exert diverse cytotoxic effects on various human cell type especially neural cell lines. In order to test our hypothesis, putative cytotoxic effects of oxidative stress due to TiO2 NPs exposure on IM9, U937 and SHSY5Y (human neuroblastoma cells) were investigated in N-acetyl cysteine (NAC), neopterin and dexamethasone pre-treated cell cultures. IM9, U937 and SHSY5Y cells were exposed to ten different concentrations of 25 and 10 nm diameter TiO2 NPs ...
Protein Binding Effects of Dopamine Coated Titanium Dioxide Shell Nanoparticles
Precision Nanomedicine
Non-targeted nanoparticles are capable of entering cells, passing through different subcellular compartments and accumulating on their surface a protein corona that changes over time. In this study, we used metal oxide nanoparticles with iron-oxide core covered with titanium dioxide shell (Fe3O4@TiO2), with a single layer of covalently bound dopamine covering the nanoparticle surface. Mixing nanoparticles with cellular protein isolates showed that these nanoparticles can form complexes with numerous cellular proteins. The addition of non-toxic quantities of nano-particles to HeLa cell culture resulted in their non-specific uptake and accumulation of protein corona on nanoparticle surface. TfRC, Hsp90 and PARP were followed as representative protein components of nanoparticle corona; each protein bound to nanoparticles with different affinity. The presence of nanoparticles in cells also mildly modulated gene expression on the level of mRNA. In conclusion, cells exposed to non-targete...