The therapeutic potential of prodigiosin as a hydrophobic anticancer agent can be enhanced by various approaches, one of which is the loading of PG into extracellular vesicles. Drug distribution and stability in aqueous media play a crucial role in targeting and accumulation, thereby enabling the attainment of therapeutically effective drug concentrations. Extracellular vesicles are nano-sized, cell-derived vesicles with a lipid bilayer membrane. Extracellular vesicles can be utilized as drug carriers for both water-soluble and non-water-soluble therapeutic agents. We hypothesized that microvesicles could effectively address the current challenges of prodigiosin delivery. Several different techniques have been developed for fabricating extracellular vesicles. These include microvesicles induction by cytochalasin B treatment as well as cell cultivation in serum depleted media. In our study, prodigiosin, like cytochalasin B, demonstrated efficacy in microvesicles formation based on protein quantification and Nanoparticle Tracking Analysis. In addition, Nanoparticle Tracking Analysis showed that vesicles from mesenchymal stem cells are more stable under ultrasound exposure. Microvesicles encapsulating prodigiosin, compared to unmodified naïve ones, demonstrated slightly increased zeta potentials and hydrodynamic diameters, which probably contributed to better stability. We demonstrated that ultrasonic treatment for the loading of prodigiosin does not significantly increase the proportion of prodigiosin-positive microvesicles in comparison with microvesicles induced with prodigiosin; moreover, this method cannot be considered as optimal due to its disadvantages, such as particle aggregation. Prodigiosin-induced and prodigiosin-loaded microvesicles from mesenchymal stem cells were significantly smaller and less polydisperse in size. Overall, prodigiosin encapsulated in extracellular vesicles might be more suitable for medical and clinical applications compared to pure forms of PG due to their cell membrane compatibility.

This article is devoted to the development of a new method for the synthesis of magnetic cobalt boride nanoparticles using a low-energy approach. The obtained nanoparticles were used to create composite materials based on industrial thermoplastic ABS. The effect of different concentrations of nanoparticles on the physical, mechanical, magnetic, and dielectric properties of composite materials was studied. It was proven that by varying the concentration of nanoparticles in the ABS composite, it is possible to control the glass transition temperature from 107.5 to 112 °C. The resulting composites demonstrated superparamagnetic behavior, which changed linearly. The permittivity of the composite remained close to that of pure ABS, but a shift in the maximum permittivity to the low-frequency region was observed with an increase in the content of nanoparticles. Thus, a method for controlling the mechanical, magnetic, and dielectric properties of a composite material has been developed, which makes it possible to use routine ABS in a wider range of applications, including electrical devices.

Background/Objectives: Current promising treatments for many diseases are based on the use of therapeutic nucleic acids, including DNA. However, the list of nanocarriers is limited due to their low biocompatibility, high cost, and toxicity. The design of synthetic building blocks for creating universal delivery systems for genetic material is an unsolved problem. In this work, we propose PAMAM dendrimers with rigid thiacalixarene core in various conformations, i.e., PAMAM-calix-dendrimers, as a platform for a supramolecular universal constructor for nanomedicine. Results: Third generation PAMAM dendrimers with a macrocyclic core in three conformations (cone, partial cone, and 1,3-alternate) were synthesized for the first time. The obtained dendrimers were capable of binding and compacting calf thymus DNA, whereby the binding efficiency improved with increasing generation, while the influence of the macrocyclic core was reduced. A dramatic effect of the macrocyclic core conformation on the hemolytic activity of PAMAM-calix-dendrimers was observed. Specifically, a notable reduction in hemotoxicity was associated with a decrease in compound amphiphilicity. Conclusions: We hope the results will help reduce financial and labor costs in developing new drug delivery systems based on dendrimers.

Hyperbranched polymers are successful nanoscale functional platforms for loading metal ions and creating promising nanomaterials for medicine. This work presents the synthesis of metal-polymer nanostructures based on a second generation hyperbranched polyester with eight terminal benzoylthiocarbamate (BTC) groups loaded with Gd(III) or Dy(III) ions. Their structure (Fourier transform infrared spectroscopy) and morphology (transmission electron microscopy), photophysical (ultraviolet-visible and luminescence spectroscopy), thermophysical, magnetic activity, relaxivity, and aggregation properties (nanoparticle tracking analysis) were studied. The formation of the metal-polymer complex is carried out by chelation of lanthanide ions -C & boxH;O and -C & boxH;S groups of the BTC fragment of polyester. Coordination units with composition Ln(III)-3BTC (Ln = Dy, Gd) were localized on the branched polymer platform. The load is three lanthanide ions per branched polyester polybenzoylthiocarbamate macromolecule. Logarithms of stability constants of complexes and composition of coordination polyhedron have been determined. The dysprosium complex is in a paramagnetic state with antiferromagnetic correlations, and the gadolinium complex is in a paramagnetic state. The relaxivity of the Dy(III) and Gd(III) complexes increased by 2.5 and 3 times, respectively, compared to their nitrates. An important achievement is the identification of rare-earth metal (REM)-controlled morphology and self-organization for Dy(III) and Gd(III) complexes with branched polyester polybenzoylthiocarbamate in solution and on the surface. Spherical nanostructures for the dysprosium complex and nanorods for the gadolinium complex were observed. Synthesized REM-loaded nanostructures with polyester polybenzoylthiocarbamates have low hemotoxicity and can be applied in biomedicine.

Cell therapy is at the forefront of biomedicine in oncology and regenerative medicine. However, there are still significant challenges to their wider clinical application such as limited efficacy, side effects, and logistical difficulties. One of the potential approaches that could overcome these problems is based on extracellular vesicles (EVs) as a cell-free therapy modality. One of the major obstacles in the translation of EVs into practice is their low yield of production, which is insufficient to achieve therapeutic amounts. Here, we evaluated two primary approaches of artificial vesicle induction in primary T cells and the SupT1 cell line—cytochalasin B as a chemical inducer and ultrasonication as a physical inducer. We found that both methods are capable of producing artificial vesicles, but cytochalasin B induction leads to vesicle yield compared to natural secretion, while ultrasonication leads to a three-fold increase in particle yield. Cytochalasin B induces the formation of vesicles full of cytoplasmic compartments without nuclear fraction, while ultrasonication induces the formation of particles rich in membranes and membrane-related components such as CD3 or HLAII proteins. The most effective approach for T-cell induction in terms of the number of vesicles seems to be the combination of anti-CD3/CD28 antibody activation with ultrasonication, which leads to a seven-fold yield increase in particles with a high content of functionally important proteins (CD3, granzyme B, and HLA II).

Significant changes in lactobacillus-derived extracellular membrane vesicles, which transfer lipids, polysaccharides, proteins, and nucleic acids, were for the first time observed to accompany the development of resistance to antibiotics (amoxicillin and clarithromycin) in vitro in the probiotic strain Lactiplantibacillus plantarum 8p-a3. The changes occur together with large-scale genome rearrangements, changes in the profile of phenotypic sensitivity to antimicrobials of various groups, and evolution of virulence. Changes in vesicles affected their structure, composition, and activity against biofilms of opportunistic bacteria. The data provide for a better understanding of the molecular mechanisms of microbial survival under selective pressure of antimicrobials, the functional potential of probiotic vesicles, and probiotic safety assessments.

Biosensor devices that include hybrid nanostructures as transducer surface modifiers meet current requirements for methods of research and determination of drugs, including antidepressants. Here, we consider the features of amperometric monoamine oxidase biosensors based on screen-printed graphite electrodes modified with nanocomposite consisting of C60/cobalt nanoparticles/amino derivative of a second-generation polyether polyol/chitosan in the determination of the tricyclic antidepressant amitriptyline. The best modifier was selected using transmission electron microscopy, scanning electron microscopy, electrochemical impedance spectroscopy, and differential pulse voltammetry. In the biosensor development, the conditions for applying the composite based on cobalt nanoparticles/amino derivative of polyether polyol to the electrode surface were varied: electrochemical deposition, sequential deposition by the layer-on-layer method, and deposition of a mixture. As an analytical signal of the biosensor, we used the peak of the electrochemical oxidation of hydrogen peroxide, which is formed during the enzymatic oxidation of serotonin under the action of monoamine oxidase. The operating principle of the biosensor is based on the inhibitory effect of amitriptyline on the catalytic activity of immobilized monoamine oxidase. For the selected modifier, the determined concentration range of amitriptyline is 1 × 10–4–1 × 10–8 mol/L and the lower limit of the determined contents is 5 × 10–9 mol/L under optimal operating conditions. Comparison of the results of the amitriptyline determination in a pharmaceutical preparation and urine that were obtained using a monoamine oxidase biosensor and the method of fluorescence polarization immunoassay (dilution of the tracer of 1 : 32, dilution of antibodies of 1 : 128, range of working concentrations from 5 × 10–8 to 5 × 10–9 mol/L), which has proven itself in the determination of medicinal substances, confirmed the correctness of the developed method.

Cellular therapy is a promising branch of biomedicine. Problems with the effectiveness and safety of these therapy can be solved by using extracellular vesicles (EV) as a cell-free modality. One of the main obstacles for technology is low yield. In a study, we tested cytochalasin B as a chemical inducer and ultrasound as a physical inducer of artificial vesicles (AVs) from primary T cells and the SupT1 cell line.

The polyol process is one of the simple, efficient and productive methods for the synthesis of metal loaded polymer composites. Functional properties of metal-polymer nanocomposites are determined by chemical composition, size and morphology of their particles. Finding effective ways to control the nanoparticle's properties during the polyol process is a crucial task. The effect of molar ratio Mn+/OHPEG on the formation of cobalt loaded metal-polymer nanocomposites during a one-pot two-component polyol process by polyethylene glycol with Mr = 4000 g·mol–1 (PEG) was studied. The PEG-based polyol process and the formation of cobalt nanophase were studied at molar ratios νCo2+/νOH(PEG) = 1:1, 1:10, 1:100 and 1:500 using UV-Vis, diffuse reflectance IR and ATR FT-IR spectroscopy, nanoparticle tracking analysis (NTA), dynamic light scattering (DLS). It was found that PEG can act as a reducing agent and stabilizing matrix for the cobalt nanophase at a ratio higher than Mn+/OHPEG= 1:10. The composition and morphology of Co/PEG nanocomposites were determined by XRD and TEM methods. Two types of spheroid particles with average diameters of 88±55 nm / 8±4 nm and 12±3 nm / 3±1 nm, respectively, represent Co/PEG nanocomposites 1:500 and 1:100. Scaly structures with a diameter of 15±5 nm are formed at a molar ratio of νCo2+/νOH(PEG) = 1:10. An increase in the Co2+ content in the PEG-based polyol process leads to the immobilized cobalt nanophase Co3O4 (1:500), Co0/CoO (1:100), CoO (1:10) in PEG. Co/PEG nanocomposites are hemocompatible. The HC50value depends on the composition and morphology of the nanoparticles.

A method for the design and synthesis of a metallopolymer composite (CoNP) based on cobalt nanoparticles using the hyperbranched polyol process was developed. It was shown that hyperbranched polyester polyols in a melted state can be both a reducing agent and a stabilizer of metal nanoparticles at the same time. The mechanism of oxidation of hyperbranched polyol was studied using diffuse reflectance IR spectroscopy. The process of oxidation of OH groups in G4-OH started from 90 °C and finished with the oxidation of aldehyde groups. The composition and properties of nanomaterials were determined with FT-IR and UV-Vis spectroscopy, Nanoparticle Tracking Analysis (NTA), thermogravimetric analysis (TG), powder X-ray diffraction (XRD), NMR relaxation, and in vitro biological tests. The cobalt-containing nanocomposite (CoNP) had a high colloidal stability and contained spheroid polymer aggregates with a diameter of 35–50 nm with immobilized cobalt nanoparticles of 5–7 nm. The values of R2 and R1 according to the NMR relaxation method for CoNPs were 6.77 mM·ms−1 × 10−5 and 4.14 mM·ms−1 × 10−5 for, respectively. The ratio R2/R1 = 0.61 defines the cobalt-containing nanocomposite as a T1 contrast agent. The synthesized CoNPs were nonhemotoxic (HC50 > 8 g/mL) multifunctional reagents and exhibited the properties of synthetic modulators of the enzymatic activity of chymosin aspartic proteinase and exhibited antimycotic activity against Aspergillus fumigatus. The results of the study show the unique prospects of the developed two-component method of the hyperbranched polyol process for the creation of colloidal multifunctional metal–polymer nanocomposites for theranostics.

The synthesis of CoNPs cobalt nanoparticles by the method of polyol- process was proposed, which consists in a high-temperature synthesis of polymer-stabilized metal nanoparticles in a matrix of a fourth-generation hyperbranched polyester polyol. Branched polyester polyol acts as both a reducing agent and a stabilizer at the same time. It has been found that the reduction of the precursor CoCl 2 with a hyperbranched polyester polyol occurs at 210°C. The introduction of NaOH into the reaction mixture makes it possible to lower the synthesis temperature by 50°C and leads to a change in the mechanism of in situ ripening CoNPs from the digestive mechanism to direct Ostwald ripening.

A procedure was developed for the single-step synthesis of a metal–polymer nanocomposite based on silver nanoparticles and second-pseudogeneration superbranched polyester functionalized along the periphery with 3-[(2-aminoethyl)amino]propionate. Under the conditions of the synthesis in the medium of H2O or DMSO, hyperbranched polyester decorated with ethylenediamine moieties can act as both a reductant of the nanoscale silver state and a stabilizer of it. The synthesized composite nanomaterial is formed by aggregates of hyperbranched polyester polyamine doped with Ag(0) nanoclusters and nanoparticles of spheroidal symmetry with a face-centered cubic crystal lattice. The hydrodynamic diameter of aggregates and the diameter of particles increase with increasing molar ratioand are 34–90 and 7–14 nm, respectively.

Polymer metal-organic framework (MOF) are a new class of hybrid porous materials that combine the ad-vantages of both organic polymers and metal-organic frameworks. In this regard, a new ligand was synthesized - a hyperbranched polyester polybenzoylthiocarbamate, the structure of which was established by IR, H-1 NMR, electron spectroscopy and elemental analysis. Complexing properties have been studied using the example of Cu(II) and Co(II) ions. The formation of metal-polymer clusters with metal ions with the participation of benzoylthiocarbamate groups of the polyester has been proved by IR, electron spectroscopy and electron microscopy. It was found that the structure of coordination sites is octahedral with tetragonal distortions. The compositions and conditional logarithms of the stability constants of the complexes were determined. (c) 2022 Elsevier B.V. All rights reserved.

New 1-cetyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide complexes with copper(II) bromide and lanthanum(III) nitrate were characterized using dynamic light scattering and transmission electron microscopy, with self-assembly and the morphological behavior elucidated. For the lanthanum(III) nitrate complex, the 3D crystal structure was characterized using X-ray diffractometry. These metallosurfactants were tested as antitumor agents, and a high cytotoxic effect comparable with doxorubicin was revealed against the M-HeLa and A-549 cell lines. Both complexes were 2 times more active toward the MCF-7 cell line than the breast cancer drug tamoxifen. The cytotoxic mechanism of complexes is assumed to be related to the induction of apoptosis through the mitochondrial pathway.

A new cobalt nanoparticles (CoNP) with a core-shell structure were obtained in a matrix of a second generation hyperbranched polyester polyol (BH20). The influence of the molar ratio Co2+ to a BH20 on the nature of stabilization centers of cobalt nanoclusters in the polymer morphology magnetic properties anti-protease activity and hemolytic activity of nanoparticles was studied. The obtained nanoparticles are superparamagnetic and have a blocking temperature of 305 K. Inhibition of the activity of the secretory aspartic protease Candida albicans in the presence of nanoparticles is 58-91%. The hemolytic activity of nanoparticles does not exceed 5%. The data obtained determine the presented cobalt nanoparticles in the matrix of the hyperbranched polyester polyol as a promising nanomaterial with low cytotoxicity for use in medicine and pharmacy.

A highly efficient hybrid adsorbent based on an industrially available, biodegradable, non-toxic linencellulose modified with hyperbranched polyesterpolybenzoylthiocarbamate has been synthesized.The synthesis was carried out using as a linkertoluene diisocyanate.The second-generation hyperbranched polyesterpolybenzoylthiocarbamate according to 1H, 13C NMR and IR spectroscopy contains 8 terminal benzoylthiocarbamate and 8 hydroxyl groups.In the first stage, the reaction of toluene diisociant with linen cellulose was carried out. By potentiometric titration, the content of toluene diisociant was found to be 27%. Then, hyperbranched polyesterpolybenzoylthiocarbamate was added to the modified linen cellulose. The content of hyperbranched polymer in cellulose, determined by the weight method, is 5%. Unreacted isocyanate groups are neutralized with isobutyl alcohol. The structure of the hybrid material is proven by IR spectroscopy. The adsorption properties of the polydentate adsorbent were studied with respect to Cu(II) ions. It was found that the adsorption capacity of the adsorbent is 6.93 mg/g. Using DSC and TGA analysis, the temperature characteristics, thermal effects, and mass loss of the obtained polydentate compound and its complexes were determined.It was shown that in an acidic medium at pH 3-4, desorption of Cu (II) and Co (II) ions occurs with the regeneration of a hybrid adsorbent.

For the first time, metal–polymer complexes have been synthesized using hyperbranched polyester polyfumaratomaleate as a matrix, the structure of which has been established by 1H NMR, IR, electron spectroscopy, and elemental analysis methods. The formation of complexes with Gd(III) and Dy(III) ions involving fumarate and maleate groups of the polyester was proved by IR and electron spectroscopy methods. It was established that the structure of the coordination units has the form of a square antiprism. The compositions and conditional logarithms of the stability constants of the complexes were determined. It was established that complexation with lanthanide ions promotes emission enhancement in the ligand.

The study of self-assembly processes in polymer solutions is the basis of a modern strategy for creating targeting systems for various substrates. In turn, the use of binary polymer/surfactant systems makes it possible to expand the range of polymers for creating drug delivery systems. This article describes the processes of formation of hybrid micelles based on carboxyl-terminal hyperbranched polyester polyol Boltorn H20-[BH20-COOH] and surfactant Triton X-100-[BH20-COOH/TX-100]. Using pH-metry, conductometry, dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and scanning electron microscopy (SEM), it was shown that at pH = 6.5, a monodisperse [BH20-COOH] associate with a hydrodynamic diameter D-h = 79 +/- 10 nm and hybrid micelles [BH20-COOH/TX-100] with D-h = 114.3 +/- 6 nm are formed. Both types of supramolecular associates are able to effectively encapsulate the anticancer drug doxorubicin. The viability analysis of HeLa and MCF-7 cells was performed in the presence of doxorubicin-loaded [BH20-COOH] and hybrid micelles [BH20-COOH/TX-100] in vitro.

This article shows the success of using the chemical reduction method, the polyol thermolytic process, the sonochemistry method, and the hybrid sonochemistry/polyol process method to design iron-based magnetically active composite nanomaterials in a hyperbranched polyester polyol matrix. Four samples were obtained and characterized by transmission and scanning electron microscopy, infrared spectroscopy and thermogravimetry. In all cases, the hyperbranched polymer is an excellent stabilizer of the iron and iron oxides nanophase. In addition, during the thermolytic process and hybrid method, the branched polyol exhibits the properties of a good reducing agent. The use of various approaches to the synthesis of iron nanoparticles in a branched polyester polyol matrix makes it possible to control the composition, geometry, dispersity, and size of the iron-based nanophase and to create new promising materials with colloidal stability, low hemolytic activity, and good magnetic properties. The NMR relaxation method proved the possibility of using the obtained composites as tomographic probes.

Electrochemical properties of two new derivatives of phenothiazine, i.e., 3,7-bis(4-aminophenylamino) phenothiazin-5-ium chloride (PhTz-(NH2)(2)) and 3,7-bis(4-carboxyphenylamino)phenothiazin-5-ium chloride (PhTz-(COOH)(2)), has been investigated on glassy carbon electrode. The pH influence on their electrode reactions was specified. The compounds studied showed complex kinetics of electrode reactions. Heterogeneous constants of the electron transfer at pH = 7.0 calculated from the Tafel plot were equal to 8.3 x 10(-4) and 7.4 x 10(-4) cm s(-1) and transfer coefficients to 0.52 and 0.36 for PhTz-(NH2)(2) and PhTz-(COOH)(2), respectively. For carboxylate derivative, significant influence of the pH of working solution on the transfer coefficient was mentioned. Based on cyclic voltammetry, quartz crystal microbalance and spectroscopy of electrochemical impedance, deposition of oxidation products was found for PhTz-(NH2)(2) and PhTz-(COOH)(2) in multiple potential cycling. The carboxylic groups critically influenced electropolymerization of appropriate compound. The formation of bonds typical for electropolymerization was also confirmed by diffusion reflectance IR spectra. The electropolymerization product exerted high electrochemical activity within a broad pH range. Heterogeneous rate constant of the electropolymerized product was found to be 4.5 x 10(-1) s(-)(1). (C) 2021 Elsevier Ltd. All rights reserved.