Search

Abstract Magnetogenetics emerges as a transformative approach for modulating cellular signaling pathways through the strategic application of magnetic fields and nanoparticles. This technique leverages the unique properties of magnetic nanoparticles (MNPs) to induce mechanical or thermal stimuli within cells, facilitating the activation of mechano- and thermosensitive proteins without the need for traditional ligand-receptor interactions. Unlike traditional modalities that often require invasive interventions and lack precision in targeting specific cellular functions, magnetogenetics offers a non-invasive alternative with the capacity for deep tissue penetration and the potential for targeting a broad spectrum of cellular processes. This review underscores magnetogenetics’ broad applicability, from steering stem cell differentiation to manipulating neuronal activity and immune responses, highlighting its potential in regenerative medicine, neuroscience, and cancer therapy. Furthermore, the review explores the challenges and future directions of magnetogenetics, including the development of genetically programmed magnetic nanoparticles and the integration of magnetic field-sensitive cells for in vivo applications. Magnetogenetics stands at the forefront of cellular manipulation technologies, offering novel insights into cellular signaling and opening new avenues for therapeutic interventions.

Abstract The treatment of tuberculosis is still a challenging process due to the widespread of pathogen strains resistant to antibacterial drugs, as well as the undesirable effects of anti-tuberculosis therapy. Hence, the development of safe and effective new anti-antitubercular agents, in addition to suitable nanocarrier systems, has become of utmost importance and necessity. Our research aims to develop liposomal vesicles that contain newly synthesized compounds with antimycobacterial action. The compound being studied is a derivative of imidazo-tetrazine named 3-(3,5-dimethylpyrazole-1-yl)-6-(isopropylthio) imidazo [1,2-b] [1,2,4,5] tetrazine compound. Several factors that affect liposomal characteristics were studied. The maximum encapsulation efficiency was 53.62 ± 0.09. The selected liposomal formulation T8* possessed a mean particle size of about 205.3 ± 3.94 nm with PDI 0.282, and zeta potential was + 36.37 ± 0.49 mv. The results of the in vitro release study indicated that the solubility of compound I was increased by its incorporation in liposomes. The free compound and liposomal preparation showed antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) at MIC value 0.94–1.88 μg/ml. We predict that the liposomes may be a good candidate for delivering new antitubercular drugs.

In this paper, the electron and magnetic state of iron placed either on the surface or in the core of TiO2 nanoparticles were investigated using magnetometric methods, electron paramagnetic resonance (EPR) and Mössbauer spectroscopy. It was demonstrated that the EPR spectra of TiO2 samples with iron atoms localized both on the surface and in the core of specific features depending on the composition and size of the nanoparticles. Theoretical calculations using the density functional theory (DFT) method demonstrated that the localization of Fe atoms on the surface is characterized by a considerably larger set of atomic configurations as compared to that in the core of TiO2 nanoparticles. Mössbauer spectra of the samples doped with Fe atoms both on the surface and in the core can be described quite satisfactorily using two and three doublets with different quadrupole splitting, respectively. This probably demonstrates that the Fe atoms on particle surface and in the bulk are in different unlike local surroundings. All iron ions, both on the surface and in the core, were found to be in the Fe3+ high-spin state.

4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were found to be obtained by the regiospecific cyclization of 2-arylhydrazinylidene-3-(polyfluoroalkyl)-3-oxoesters with hydrazines, by the azo coupling of 4-nonsubstituted pyrazol-5-oles with aryldiazonium chlorides or by the firstly discovered acid-promoted self-condensation of 2-arylhydrazinylidene-3-oxoesters. All the 4-AHPs had an acceptable ADME profile. Varying the substituents in 4-AHPs promoted the switching or combining of their biological activity. The polyfluoroalkyl residue in 4-AHPs led to the appearance of an anticarboxylesterase action in the micromolar range. An NH-fragment and/or methyl group instead of the polyfluoroalkyl one in the 4-AHPs promoted antioxidant properties in the ABTS, FRAP and ORAC tests, as well as anti-cancer activity against HeLa that was at the Doxorubicin level coupled with lower cytotoxicity against normal human fibroblasts. Some Ph-N-substituted 4-AHPs could inhibit the growth of N. gonorrhoeae bacteria at MIC 0.9 μg/mL. The possibility of using 4-AHPs for cell visualization was shown. Most of the 4-AHPs exhibited a pronounced analgesic effect in a hot plate test in vivo at and above the diclofenac and metamizole levels except for the ones with two chlorine atoms in the aryl group. The methylsulfonyl residue was proved to raise the anti-inflammatory effect also. A mechanism of the antinociceptive action of the 4-AHPs through blocking the TRPV1 receptor was proposed and confirmed using in vitro experiment and molecular docking.

Linked to Alzheimer’s disease (AD), amyloids and tau-protein are known to contain a large number of cysteine (Cys) residues. In addition, certain levels of some common biogenic thiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH), etc.) in biological fluids are closely related to AD as well as other diseases. Therefore, probes with a selective interaction with the above-mentioned thiols can be used for the monitoring and visualizing changes of (bio)thiols in the biological fluids as well as in the brain of animal models of Alzheimer’s disease. In this study, new Eu(III), Tb(III), Gd(III) and Sm(III) complexes of 2,2′-bipyridine ligands containing TEMPO fragments as receptor units for (bio)thiols are reported. The presence of free radical fragments of the ligand in the complexes was proved by using the electronic paramagnetic resonance (EPR) method. Among all the complexes, the Eu(III) complex turned out to be the most promising one as luminescence- and spin-probe for the detection of biogenic thiols. The EPR and fluorescent titration methods showed the interaction of the resulting complex with free Cys and GSH in solution. To study the practical applicability of the probes for the monitoring of AD in-vivo, by using the above-mentioned Eu(III)-based probe, the staining of the brain of mice with amyloidosis and Vero cell cultures supplemented with the cysteine-enriched medium was studied as well as the fluorescence titration of Bovine Serum Albumin, BSA (as the model for the thiol moieties containing protein), was carried out. Based on the results of fluorescence titration, the formation of a non-covalent inclusion complex between the above-mentioned Eu(III) complex and BSA was suggested.

A series of new composite materials based on Fe3O4 magnetic nanoparticles coated with SiO2 (or aminated SiO2) were synthesized. It has been shown that the use of N-(phosphonomethyl)iminodiacetic acid (PMIDA) to stabilize nanoparticles before silanization ensures the increased content of a SiO2 phase in the Fe3O4@SiO2 nanocomposites (NCs) in comparison with materials obtained under similar conditions, but without PMIDA. It has been demonstrated for the first time that the presence of PMIDA on the surface of NCs increases the level of Dox loading due to specific binding, while surface modification with 3-aminopropylsilane, on the contrary, significantly reduces the sorption capacity of materials. These regularities were in accordance with the results of quantum chemical calculations. It has been shown that the energies of Dox binding to the functional groups of NCs are in good agreement with the experimental data on the Dox sorption on these NCs. The mechanisms of Dox binding to the surface of NCs were proposed: simultaneous coordination of Dox on the PMIDA molecule and silanol groups at the NC surface leads to a synergistic effect in Dox binding. The synthesized NCs exhibited pH-dependent Dox release, as well as dose-dependent cytotoxicity in in vitro experiments. The cytotoxic effects of the studied materials correspond to their calculated IC50 values. NCs with a SiO2 shell obtained using PMIDA exhibited the highest effect. At the same time, the presence of PMIDA in NCs makes it possible to increase the Dox loading, as well as to reduce its desorption rate, which may be useful in the design of drug delivery vehicles with a prolonged action. We believe that the data obtained can be further used to develop stimuli-responsive materials for targeted cancer chemotherapy.

Pharmacological interventions which could be hepatoprotective, depending on bioavailability, anti-inflammatory and macrophage-targeting potential of drugs, are still at early preclinical stages. Existing evidence from many animal models of liver injury, as well as from human data, indicate that pharmacological and/or phytochemical interventions have limited impact on liver recovery. Recent studies on stem cell therapies focused on different cell subsets involved in tissue repair, including monocytes/macrophages and bone marrow cells migrating to the injured liver. Partial hepatectomy (PH) resulted in a rapid increase of monocytes/macrophages in bone marrow and liver, which could be further enhanced by prior treatment of animals with sodium phthalhydrazide. Increased number of proliferating Ki67+ hepatocytes, increased total protein and albumin content in regenerating liver, recruitment of CD172a+ macrophages and more differentiated CD45lowCD117+ bone marrow cells, could be further promoted by the treatment of animals with 2 mg/kg b.w. phthalhydrazide, considered immunomodulatory, antioxidant and macrophage-silencing. Phenotypic polarization of macrophages can possibly explain the macrophage reparative capacities, protective against liver injury. Enhanced macrophage cell recruitment from bone marrow to regenerating liver can be possibly one of important events in hepatic recovery.

The method of Fe3O4 magnetic nanoparticle synthesis by co-precipitation, modification by 3-aminopropylsilane and conjugation with pH-(low)-insertion peptide (pHLIP) is reported. The characterization of nanoparticles by scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, elemental and thermogravimetric analyses as well as dynamic light scattering and z-potential measurements is provided. The effect of nanoparticles on the viability of mouse and human peripheral blood mononuclear cells is tested by flow cytometry. The experimental details of nanoparticle administration to tumor-bearing mice, magnetic resonance imaging scanning as well as subsequent tumor sample collection and their processing for transmission electron microscopy, inductively coupled plasma atomic emission spectroscopy, histological and immunohistochemical analyses are described. Biodistribution of the nanoparticles in mice and blood serum analysis data for experimental animals are given. The data are useful for an experiment workflow design and for the development of theranostic systems based on magnetic nanoparticles. Keywords: pHLIP, Iron oxide magnetic nanoparticle, Nanoparticle characterization, Tumor, Biodistribution, Cytotoxicity