A two-armed probe for in-cell DEER measurements on proteins. - In: Chemistry - a European journal, ISSN 1521-3765, Bd. 26 (2020), 71, S. 17128-17133
The application of double electron-electron resonance (DEER) with site-directed spin labeling (SDSL) to measure distances in proteins and protein complexes in living cells puts rigorous restraints on the spin-label. The linkage and paramagnetic centers need to resist the reducing conditions of the cell. Rigid attachment of the probe to the protein improves precision of the measured distances. Here, three two-armed GdIII complexes, GdIII-CLaNP13a/b/c were synthesized. Rather than the disulfide linkage of most other CLaNP molecules, a thioether linkage was used to avoid reductive dissociation of the linker. The doubly GdIII labeled N55C/V57C/K147C/T151C variants of T4Lysozyme were measured by 95 GHz DEER. The constructs were measured in vitro, in cell lysate and in Dictyostelium discoideum cells. Measured distances were 4.5 nm, consistent with results from paramagnetic NMR. A narrow distance distribution and typical modulation depth, also in cell, indicate complete and durable labeling and probe rigidity due to the dual attachment sites.
https://doi.org/10.1002/chem.202002743
Graphene oxide influences on mechanical properties and drug release ability of hydroxyapatite based composite material. - In: Nanomaterials in biomedical application and bionsensors (NAP-2019), (2020), S. 139-149
Bioactive composite material based on hydroxyapatite (HA), sodium alginate (Alg) with different content of graphene oxide (GO) was synthesized by the wet chemistry method and characterized by TEM, XRD, FTIR, HPLC analysis. Introduced the GO nanoparticles, as well as Ca2+ ions, as cross-linker of Alg macromolecules by the beads formation, lead to enhancement of the composites mechanical properties. HA-Alg-GO10 sample with GO content of 0.004% in relation to the HA powder has a much higher Youngs modulus (1325 MPa) in comparison with GO-free HA-Alg composite (793 MPa), as well as steel sample of the same size (˜706 MPa). The addition of GO reduces the degree of the composites swelling in a phosphate buffered saline for 43% and enhances the beads shape stability. Chlorhexidine bigluconate release from GO containing samples lasts for 48 h longer according to HPLC study. The findings clear demonstrate the potential possibility of applications of the HA-Alg-GO composite material in bioengineering of bone tissue to fill bone defects of various geometries with the function of prolonged release of the drug. It is assumed that HA-Alg-GO composite material can be used in 3D modeling of areas of bone tissue that have to bear a mechanical load.
Sensor micro and nanoparticles for microfluidic application. - In: Applied Sciences, ISSN 2076-3417, Bd. 10 (2020), 23, 8353, S. 1-37
Micro and nanoparticles are not only understood as components of materials but as small functional units too. Particles can be designed for the primary transduction of physical and chemical signals and, therefore, become a valuable component in sensing systems. Due to their small size, they are particularly interesting for sensing in microfluidic systems, in microarray arrangements and in miniaturized biotechnological systems and microreactors, in general. Here, an overview of the recent development in the preparation of micro and nanoparticles for sensing purposes in microfluidics and application of particles in various microfluidic devices is presented. The concept of sensor particles is particularly useful for combining a direct contact between cells, biomolecules and media with a contactless optical readout. In addition to the construction and synthesis of micro and nanoparticles with transducer functions, examples of chemical and biological applications are reported.
https://doi.org/10.3390/app10238353
Emerging structural and interfacial features of particulate polymers at the nanoscale. - In: Langmuir, ISSN 1520-5827, Bd. 36 (2020), 44, S. 13125-13143
Particulate polymers at the nanoscale are exceedingly promising for diversified functional applications ranging from biomedical and energy to sensing, labeling, and catalysis. Tailored structural features (i.e., size, shape, morphology, internal softness, interior cross-linking, etc.) determine polymer nanoparticles' impact on the cargo loading capacity and controlled/sustained release, possibility of endocytosis, degradability, and photostability. The designed interfacial features, however (i.e., stimuli-responsive surfaces, wrinkling, surface porosity, shell-layer swellability, layer-by-layer surface functionalization, surface charge, etc.), regulate nanoparticles interfacial interactions, controlled assembly, movement and collision, and compatibility with the surroundings (e.g., solvent and biological environments). These features define nanoparticles' overall properties/functions on the basis of homogeneity, stability, interfacial tension, and minimization of the surface energy barrier. Lowering of the resultant outcomes is directly influenced by inhomogeneity in the structural and interfacial design through the structure-function relationship. Therefore, a key requirement is to produce well-defined polymer nanoparticles with controlled characteristics. Polymers are amorphous, flexible, and soft, and hence controlling their structural/interfacial features through the single-step process is a challenge. The microfluidics reaction strategy is very promising because of its wide range of advantages such as efficient reactant mixing and fast phase transfer. Overall, this feature article highlights the state-of-the-art synthetic features of polymer nanoparticles with perspectives on their advanced applications.
https://doi.org/10.1021/acs.langmuir.0c02566
Modeling of single-walled carbon nanotube binding to nitric oxide synthase and guanylate cyclase molecular structures. - In: Neurophysiology, ISSN 1573-9007, Bd. 52 (2020), 2, S. 110-115
Previously, we have demonstrated that water dispersible single-walled carbon nanotubes (SWCNTs) may be used in low therapeutic doses in antihypertensive therapy as promising agents capable of activating constitutive nitric oxide synthase (NOS) in spontaneously hypertensive rats, thus increasing the NO production in central and peripheral elements of the cardiovascular system [1]. Here we confirm this effect by docking and molecular dynamics simulations, clearly showing that SWCNTs may interact with NOS and guanylate cyclase molecular structures.
https://doi.org/10.1007/s11062-020-09859-0
Systemic administrations of water-dispersible single-walled carbon nanotubes: activation of NOS in spontaneously hypertensive rats. - In: Neurophysiology, ISSN 1573-9007, Bd. 52 (2020), 2, S. 101-109
Priority data have been obtained on the effects of repeated systemic administrations of water-dispersible single-walled carbon nanotubes (SWCNTs) to spontaneously hypertensive rats with respect to constitutive NO-synthase (cNOS). As is known, NO is an inhibitory transmitter in the cardiovascular system. It was found that the systemic (i.p., subcutaneous, and i.m.) introductions of SWCNTs during two weeks resulted in considerable elevations of the NO2- level (a marker of NO bioavailability) in the blood of experimental hypertensive animals. Thus, SWCNTs may be used in the future for antihypertensive therapy as a novel agent capable of activating cNOS and, thus, increasing the NO production in central and peripheral elements of the cardiovascular system.
https://doi.org/10.1007/s11062-020-09858-1
C60 fullerene governs doxorubicin effect on metabolic profile of rat microglial cells in vitro. - In: Molecular pharmaceutics, ISSN 1543-8392, Bd. 17 (2020), 9, S. 3622-3632
Im Titel ist "60" tiefgestellt
Background: C60 fullerenes and their derivatives are actively investigated for the use in neuroscience. Applications of these nanoscale materials require the examination of their interaction with different neural cells, especially with microglia, because these cells, like other tissue resident phagocytes, are the earliest and most sensitive responders to nanoparticles. The aim of this study was to investigate the effect of C60 fullerene and its nanocomplex with doxorubicin (Dox) on the metabolic profile of brain-resident phagocytes - microglia - in vitro. Methods: Resting microglial cells from adult male Wistar rats were used in experiments. Potential C60 fullerene targets in microglial cells were studied by computer simulation. Microglia oxidative metabolism and phagocytic activity were examined by flow cytometry. Griess reaction and arginase activity colorimetric assay were used to explore arginine metabolism. Results: C60 fullerene when used alone did not influence microglia oxidative metabolism and phagocytic activity but shifted arginine metabolism toward the decrease of NO generation. Complexation of C60 fullerene with Dox (C60-Dox) potentiated the ability of the latter to stimulate NO generation. Conclusion: The capability of C60 fullerenes used alone to cause anti-inflammatory shift of microglia arginine metabolism makes them a promising agent for the correction of neuroinflammatory processes involved in neurodegeneration. The potentiating action of C60 fullerene on the immunomodulatory effect of Dox allows us to consider the C60 molecule as an attractive vehicle for this antitumor agent.
https://doi.org/10.1021/acs.molpharmaceut.0c00691
Evaluation of the biocompatibility of water-soluble pristine 60 fullerenes in rabbit. - In: BioNanoScience, ISSN 2191-1649, Bd. 10 (2020), 3, S. 721-730
Im Titel ist "60" tiefgestellt
C60 fullerenes have proved their therapeutic effects and efficacy by the results of countless experiments. For further usage of these nanoparticles, the systematic toxicological investigations are required. Blood compatibility should be studied for C60 fullerenes due to the potential blood contact. Currently, available data is not systematic and has not provided insights into possible side effects of C60 fullerenes on blood components. In this study, water-soluble pristine C60 fullerenes were tested in vitro to assess their biocompatibility in rabbit. The blood compatibility has been evaluated looking at the impact of C60 fullerenes on erythrocyte integrity, platelet aggregation, and some blood factors involved in coagulation. Our results revealed that C60 fullerenes cannot elicit hemolysis at studied concentrations and did not show any effect on coagulation process. C60 fullerenes in concentration-dependent manner increased ADP-dependent platelet aggregation and changed the key kinetic parameters of these processes. C60 fullerenes inhibited thrombin amidolytic activity but did not affect the activities of other studied coagulation factors. The prothrombotic property of C60 fullerenes could be the potential risk factor that leads to enhancement of vascular thrombosis. The ability of fullerene to inhibit thrombin activity is important for the pharmacological use of these carbon nanoparticles as anticoagulant agents.
https://doi.org/10.1007/s12668-020-00762-w
New nanostructured apatite-type (Na+,Zn2+,CO32-)-doped calcium phosphates : Preparation, mechanical properties and antibacterial activity. - In: Journal of molecular structure, ISSN 0022-2860, Bd. 1222 (2020), 128932
Im Titel sind "+", "2+" und "2-" hochgestellt, "3" tiefgestellt
Nanoparticles with the sizes in the range (20-30) nm of apatite-type Na+,Zn2+,CO32--doped calcium phosphates were prepared from aqueous solution of Na+-Ca2+-Zn2+-NO3--CO32--PO43- system at molar ratios Ca2+/PO43- =1.67, CО32-/РО43- = 1, Zn2+:Ca2+ = 1:100 or 2:100. The elemental analysis showed growth of Zn2+ content in composition of samples from 0.61 to 1.95 wt% at increasing of Zn2+ amount in an initial solution. According to FTIR and Raman data, B-type substitution of PO43- by CO32- realized in apatite-type calcium phosphates. The mechanical properties study for prepared phases showed the dependence of Young's modulus and compressive strength on Zn2+ amount in their composition. Growth of S. epidermidis after the contact with synthesized apatite containing Na+ (0.25 wt%), Zn2+ (0.61 wt%) and CO32- (1.18 wt%) was significantly delayed with an extension of lag time from 1 to 13-14 h. The prepared sample can be considered as a new prospective biomaterial with antibacterial potential.
https://doi.org/10.1016/j.molstruc.2020.128932
Water-soluble pristine C60 fullerene inhibits liver alterations associated with hepatocellular carcinoma in rat. - In: Pharmaceutics, ISSN 1999-4923, Bd. 12 (2020), 9, 794, S. 1-20
Richtiger Name des Verfassers: Eric Täuscher
https://doi.org/10.3390/pharmaceutics12090794