Nutrient or energy deprivation, especially glucose restriction, is a promising anticancer therapeutic approach. However, establishing a precise and potent deprivation strategy remains a formidable task. The Golgi morphology is crucial in maintaining the function of transport proteins (such as GLUT1) driving glycolysis. Thus, in this study, we present a "Golgi-customized Trojan horse" based on tellurium loaded with apigenin (4',5,7-trihydroxyflavone) and human serum albumin, which was able to induce GLUT1 plasma membrane localization disturbance via Golgi dispersal leading to the inhibition of tumor glycolysis. Diamond-shaped delivery system can efficiently penetrate into cells as a gift like Trojan horse, which decomposes into tellurite induced by intrinsically high H2O2 and GSH levels. Consequently, tellurite acts as released warriors causing up to 3.8-fold increase in Golgi apparatus area due to the down-regulation of GOLPH3. Further, this affects GLUT1 membrane localization and glucose transport disturbance. Simultaneously, apigenin hinders ongoing glycolysis and causes significant decrease in ATP level. Collectively, our "Golgi-customized Trojan horse" demonstrates a potent antitumor activity because of its capability to deprive energy resources of cancer cells. This study not only expands the applications of tellurium-based nanomaterials in the biomedicine but also provides insights into glycolysis restriction for anticancer therapy.
- MeSH
- apigenin * aplikace a dávkování farmakologie MeSH
- buněčná membrána * metabolismus účinky léků MeSH
- glukosa metabolismus MeSH
- glykolýza * účinky léků MeSH
- Golgiho aparát * metabolismus účinky léků MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie metabolismus patologie MeSH
- přenašeč glukosy typ 1 * metabolismus MeSH
- protinádorové látky aplikace a dávkování farmakologie MeSH
- telur * aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tellurite resistance gene clusters have been identified in numerous pathogenic bacteria, including clinical isolates of Escherichia coli. The rareness of tellurium in host organisms and the noncontaminated environment raises a question about the true functionality of tellurite resistance gene clusters in pathogenesis and their possible contribution to bacterial fitness. The study aims to point out the beneficial effects of the tellurite resistance gene cluster of pathogenic bacteria to survive in ROS-rich environments. Here, we analysed the bacterial response to oxidative stress conditions with and without tellurite resistance gene clusters, which are composed of terWY1XY2Y3 and terZABCDEF genes. By measuring the levels of protein carbonylation, lipid peroxidation, and expression changes of oxidative stress genes upon oxidative stress, we propose a tellurite resistance gene cluster contribution to the elimination of oxidative damage, potentially increasing fitness and resistance to reactive oxygen species during macrophage attack. We have shown a different beneficial effect of various truncated versions of the tellurite resistance gene cluster on cell survival. The terBCDEF genes increased the survival of E. coli strain MC4100 by 13.21%, terW and terZABCDEF by 10.09%, and terWY1XY2Y3 and terZABCDEF by 25.57%, respectively. The ability to survive tellurite treatment is the most significant at 44.8% in wild clinical strain KL53 compared to laboratory strain E. coli MC4100 due to a complete wild-type plasmid presence.
- MeSH
- Escherichia coli * MeSH
- multigenová rodina MeSH
- oxidační stres MeSH
- telur * farmakologie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
With the goal to investigate biological phenomena at a single-cell level, we designed, synthesized and tested a molecular probe based on Förster resonance energy transfer (FRET) between a highly luminescent quantum dot (QD) as a donor and a fluorophore or fluorescence quencher as an acceptor linked by a specific peptide. In principle, QD luminescence, effectively dissipated in the probe, is switched on after the cleavage of the peptide by a protease and the release of the quencher. We proposed a novel synthesis strategy of a probe. A two-step synthesis consists of: (i) Conjugation of CdTe QDs functionalized by -COOH groups of succinic acid on the nanoparticle surface with the designed specific peptide (GTADVEDTSC) using a ligand-exchange approach; (ii) A fast, high-yield reaction of amine-reactive succinimidyl group on the BHQ-2 quencher with N-terminal of the peptide. This way, any crosslinking between individual nanoparticles and any nonspecific conjugation bonds are excluded. The analysis of the product after the first step proved a high reaction yield and nearly no occurrence of unreacted QDs, a prerequisite of the specificity of our luminescent probe. Its parameters evaluated as Michaelis-Menten description of enzymatic kinetics are similar to products published by other groups. Our research is focused on the fluorescence microscopy analyses of biologically active molecules, such as proteolytic active caspases, playing important roles in cell signaling regulations in normal and diseased states. Consequently, they are attractive targets for clinical diagnosis and medical therapy. The ultimate goal of our work was to synthesize a new QD luminescent probe for a long-time quantitative monitoring of active caspase-3/7 distribution in apoptotic osteoblastic MC3T3-E1 cells treated with camptothecin. As a result of comparison, our synthetized luminescent probe provides longer imaging times of caspases than commercial products. The probe proved the stability of the luminescence signal inside cells for more than 14 days.
BACKGROUND: Cadmium-Zinc-Telluride (CZT) technology allows use of low activities of radiopharmaceuticals. The aim was to verify the values of left ventricular volume parameters, obtained via ultra-low-dose thallium Single Photon Emission Computed Tomography (SPECT) using a CZT camera. METHODS AND RESULTS: Forty-five patients referred for an assessment of myocardial perfusion or viability imaging were examined using CZT-SPECT and 1.5 T magnetic resonance (MRI) scanner. The ultra-low-dose protocol with 0.5 Mbq 201-Tl per kg of body weight was used. The values of end-systolic (ESV) and end-diastolic volumes (EDV), left ventricular ejection fraction (EF) and myocardial mass (MM) were assessed using both techniques. A very good correlation was found between the EF, ESV, and EDV values assessed with CZT-SPECT and cardiac magnetic resonance MRI; the Pearson coefficients were 0.86, 0.95, and 0.91, respectively. A moderate correlation was found for myocardial mass, r = 0.57. Compared to MRI, SPECT systematically overestimated ESV and MM, while it underestimates the EF, with P ≤ .001 in all cases. There was no difference in EDV estimation. CONCLUSIONS: Left ventricular volumes and ejection fraction assessed via ultra-low-dose CZT-SPECT showed very good correlation with the values obtained by MRI. A moderate correlation was found for myocardial mass.
- MeSH
- funkce levé komory srdeční * MeSH
- jednofotonová emisní výpočetní tomografie * metody MeSH
- kadmium MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- radioizotopy thallia MeSH
- telur MeSH
- tepový objem MeSH
- zinek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Selenium is an essential trace element that is crucial for cellular antioxidant defense against reactive oxygen species (ROS). Recently, many selenium-containing compounds have exhibited a wide spectrum of biological activities that make them promising scaffolds in Medicinal Chemistry, and, in particular, in the search for novel compounds with anticancer activity. Similarly, certain tellurium-containing compounds have also exhibited substantial biological activities. Here we provide an overview of the biological activities of seleno- and tellurocompounds including chemopreventive activity, antioxidant or pro-oxidant activity, modulation of the inflammatory processes, induction of apoptosis, modulation of autophagy, inhibition of multidrug efflux pumps such as P-gp, inhibition of cancer metastasis, selective targeting of tumors and enhancement of the cytotoxic activity of chemotherapeutic drugs, as well as overcoming tumor drug resistance. A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.
- MeSH
- chemorezistence MeSH
- lidé MeSH
- mnohočetná léková rezistence MeSH
- nádory * farmakoterapie MeSH
- nanočástice * MeSH
- protinádorové látky * chemie farmakologie terapeutické užití MeSH
- reaktivní formy kyslíku MeSH
- selen * chemie farmakologie terapeutické užití MeSH
- telur chemie farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Quantum dots (QDs) have a broad range of applications in cell biolabeling, cancer treatment, metastasis imaging, and therapeutic drug monitoring. Despite their wide use, relatively little is known about their influence on other molecules. Interactions between QDs and proteins can influence the properties of both nanoparticles and proteins. The effect of mercaptosuccinic acid-capped CdTe QDs on intercellular copper-zinc superoxide dismutase (SOD1)-one of the main enzymatic antioxidants-was investigated. Incubation of SOD1 with QDs caused an increase in SOD1 activity, unlike in the case of CdCl2, which inhibited SOD1. Moreover, this effect on SOD1 increased with the size and potential of QDs, although the effect became clearly visible in higher concentrations of QDs. The intensity of QD-SOD1 fluorescence, analyzed with the use of capillary electrophoresis with laser-induced fluorescence detection, was dependent on SOD1 concentration. In the case of green QDs, the fluorescence signal decreased with increasing SOD1 concentration. In contrast, the signal strength for Y-QD complexes was not dependent on SOD1 dilutions. The migration time of QDs and their complexes with SOD1 varied depending on the type of QD used. The migration time of G-QD complexes with SOD1 differed slightly. However, in the case of Y-QD complexes with SOD1, the differences in the migration time were not dependent on SOD concentration. This research shows that QDs interact with SOD1 and the influence of QDs on SOD activity is size-dependent. With this knowledge, one might be able to control the activation/inhibition of specific enzymes, such as SOD1.
The implementation of quantum dots in analytical chemistry has already advanced from basic research activities to routine applications of commercially available fluorescent agents present in sophisticated assays kits. Nevertheless, a further development of new preparation and characterization methods of nanoparticles is still required to increase the sensitivity of analytical methods substantially. Thus, in many bioanalytical applications, important molecules such as DNA, proteins, and antibodies are routinely conjugated with fluorescent tags to reach even the absolute sensitivity, that is, the capability to detect a single molecule in complex matrices. Semiconductor quantum dots have already proved to be suitable components of highly luminescent tags, probes, and sensors with broad applicability in analytical chemistry. Quantum dots provide high extinction coefficients together with wide ranges of excitation wavelengths, size- and composition-tunable emissions, narrow and symmetric emission spectra, good quantum yields, relatively long size-dependent luminescence lifetime, and low photobleaching. Most of these properties are superior when compared with conventional organic fluorescent dyes. In this chapter, optimized procedures for the preparation of water-dispersed CdTe quantum dots; their coatings and conjugation reactions with antibodies, DNA, and macrocycles; and their analyses by capillary electrophoresis are described. The potential of capillary electrophoresis for fast analyses of nanoparticles, their conjugates with antibodies and immunocomplexes with targeted antigens, is demonstrated as an example.
- MeSH
- elektroforéza kapilární metody MeSH
- fluorescenční barviva chemie MeSH
- kvantové tečky chemie MeSH
- luminiscenční měření metody MeSH
- nanočástice MeSH
- nanotechnologie MeSH
- proteiny chemie MeSH
- protilátky chemie MeSH
- rezonanční přenos fluorescenční energie metody MeSH
- sloučeniny kadmia chemie MeSH
- telur chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this study, a model crop plant white mustard (Sinapis alba L.) was treated with an aqueous dispersion of silica-coated CdTe quantum dots (CdTe/SiO2 QDs) in a 72-h short-term toxicity test. The toxicity was established via measurements of (i) the root length and (ii) the chlorophyll fluorescence. These results were compared to two other sources of cadmium, free Cd ions (CdCl2) and prime un-shell nanoparticles CdTe QDs. Tested compounds were applied in concentrations representing 20 and 200 μM Cd. The uptake and translocation of Cd were investigated using inductively coupled plasma optical emission spectrometry (ICP-OES) and the spatial Cd distribution was investigated in detail applying laser induced breakdown spectroscopy (LIBS). The LIBS maps with a lateral resolution of 100 μm were constructed for the whole plants, and maps with a lateral resolution of 25 μm (micro-LIBS arrangement) were used to analyse only the most interesting parts of plants with Cd presence (e.g. root tips or a part crossing the root into the above-ground part). Our results show that the bioaccumulation patterns and spatial distribution of Cd in CdTe/SiO2 QDs-treated plants differ from the plants of positive control and CdTe QDs. Fluorescence microscopy photographs revealed that CdTe/SiO2 became adsorbed onto the plant surface in comparison to CdTe QDs. Further, a physico-chemical characterization of QDs before and after the test exposure showed only minor changes in the nanoparticle diameters and no tendencies of QDs for agglomeration or aggregation during the exposure.
To ensure food safety and to prevent unnecessary foodborne complications this study reports fast, fully automated process for histamine determination. This method is based on magnetic separation of histamine with magnetic particles and quantification by the fluorescence intensity change of MSA modified CdSe Quantum dots. Formation of Fe2O3 particles was followed by adsorption of TiO2 on their surface. Magnetism of developed probe enabled rapid histamine isolation prior to its fluorescence detection. Quantum dots (QDs) of approx. 3 nm were prepared via facile UV irradiation. The fluorescence intensity of CdSe QDs was enhanced upon mixing with magnetically separated histamine, in concentration-dependent manner, with a detection limit of 1.6 μM. The linear calibration curve ranged between 0.07 and 4.5 mM histamine with a low LOD and LOQ of 1.6 μM and 6 μM. The detection efficiency of the method was confirmed by ion exchange chromatography. Moreover, the specificity of the sensor was evaluated and no cross-reactivity from nontarget analytes was observed. This method was successfully applied for the direct analysis of histamine in white wine providing detection limit much lower than the histamine maximum levels established by EU regulation in food samples. The recovery rate was excellent, ranging from 84 to 100% with an RSD of less than 4.0%. The main advantage of the proposed method is full automation of the analytical procedure that reduces the time and cost of the analysis, solvent consumption and sample manipulation, enabling routine analysis of large numbers of samples for histamine and highly accurate and precise results.
- MeSH
- fluorescence MeSH
- fluorescenční barviva chemie MeSH
- fluorescenční spektrometrie metody MeSH
- histamin analýza MeSH
- kontaminace potravin analýza MeSH
- kovové nanočástice chemie MeSH
- kvantové tečky chemie MeSH
- limita detekce MeSH
- magnetické jevy MeSH
- silany chemie MeSH
- sloučeniny kadmia chemie MeSH
- telur chemie MeSH
- titan chemie MeSH
- víno analýza MeSH
- železité sloučeniny chemie MeSH
- Publikační typ
- časopisecké články MeSH
