Polymer Network Comprised of Steroidal Rotors as a Promising Storage Material.

The front cover artwork is provided by Dr habil. Izabella Jastrzebska's group from the University of Bialystok, Poland. The image shows a polymeric network with molecular rotors (MR) as crosslinks. The MR rotation is slowed or inhibited when a molecule of stored gas is placed inside the polymer material. Read the full text of the Research Article at 10.1002/cphc.202300793.

Polymer network comprised of steroidal rotors as promising storage material.

In this paper, we report a new generation of polymeric networks as potential functional material based on changes in molecular dynamics in the solid state. The material is obtained by free radical polymerization of a diacrylate derivative bearing a steroid (stator) and a 1,4-diethynyl-phenylene-d4 fragment (rotator). Polymer research using the PALS technique complements the knowledge about nanostructural changes occurring in the system in the temperature range -115 °C - +190 °C. It indicates the presence of two types of free nanovolumes in the system and the occurrence of phase transitions. The polymer is characterized using 1 H NMR, 2 H Solid Echo NMR, ATR-FTIR and Raman spectroscopies, thermal analysis, and porosimetry. It is proved that the applied procedure leads to the formation of a novel porous organic material containing multiple molecular rotors.

Membrane-Active Thermoresponsive Block Copolymers Containing a Diacylglycerol-Based Segment: RAFT Synthesis, Doxorubicin Encapsulation, and Evaluation of Cytotoxicity against Breast Cancer Cells.

Herein, we report the formation of drug delivery systems from original thermoresponsive block copolymers containing lipid-based segments. Two acrylate monomers derived from palmitic- or oleic-acid-based diacylglycerols (DAGs) were synthesized and polymerized by the reversible addition-fragmentation chain transfer (RAFT) method. Well-defined DAG-based polymers with targeted molar masses and narrow molar mass distributions were next used as macro-chain transfer agents (macro-CTAs) for the polymerization of N-isopropylacrylamide (NIPAAm) or N-vinylcaprolactam (NVCL). The obtained amphiphilic block copolymers were formed into polymeric nanoparticles (PNPs) with and without encapsulated doxorubicin and characterized. Their biological assessment indicated appropriate cytocompatibility with the representatives of normal cells. Furthermore, compared to the free drug, increased cytotoxicity and apoptosis or necrosis induction in breast cancer cells was documented, including a highly aggressive and invasive triple-negative MDA-MB-231 cell line.

Investigation of Magnetic Electrodes in Conducting Polymeric Materials: Electrochemical Properties of a Fullerene[C60 ]-Pd Polymer and Iron Oxide Magnetic Nanocomposite.

A composite of iron oxide magnetic nanoparticles and coordination fullerene polymer (C60 Pd3 )n is formed by chemical deposition of spherical polymer nanoparticles on iron oxide magnetic nanoparticles in benzene containing C60 and Pd(0) complex. The composition of the composite can be controlled by the amount of magnetite and concentration of polymerization precursors as well as the time of polymerization. The magnetic composite material Fe3 O4 -γFe2 O3 /(C60 Pd3 )n is used as a model system to investigate its deposition on a magnetic electrode and its electrochemical properties. The iron oxide magnetic nanoparticles ensure both the magnetic activity of the composite and its nanostructured morphology. Both of these factors are responsible for the enhancement of the electrochemical activity of the polymer phase forming the composite in comparison to the pure polymer material deposited on the same magnetic electrode. In the magnetic field of the electrode, the composite undergoes permanent and strong bonding with the surface of the electrode. The nanostructured morphology of the Fe3 O4 -γFe2 O3 /(C60 Pd3 )n composite also provides very good capacitive properties.

Magnetic Particles with Polymeric Shells Bearing Cholesterol Moieties Sensitize Breast Cancer Cells to Low Doses of Doxorubicin.

One of the promising strategies for improvement of cancer treatment is application of a combination therapy. The aim of this study was to investigate the anticancer activity of nanoformulations containing doxorubicin and iron oxide particles covered with polymeric shells bearing cholesterol moieties. It was postulated that due to high affinity to cell membranes, particles comprising poly(cholesteryl acrylate) can sensitize cancer cells to doxorubicin chemotherapy. The performed analyses revealed that the developed systems are effective against the human breast cancer cell lines MCF-7 and MDA-MB-231 even at low doses of the active compound applied (0.5 µM). Additionally, high compatibility and lack of toxicity of the tested materials against human red blood cells, immune (monocytic THP-1) cells, and cardiomyocyte H9C2(2-1) cells was demonstrated. Synergistic effects observed upon administration of doxorubicin with polymer-iron oxide hybrids comprising poly(cholesteryl acrylate) may provide an opportunity to limit toxicity of the drug and to improve its therapeutic efficiency at the same time.

Spectroscopic and Structural Study of a New Conducting Pyrazolium Salt.

The increase in conductivity with temperature in 1H-pyrazol-2-ium 2,6-dicarboxybenzoate monohydrate was analyzed, and the influence of the mobility of the water was discussed in this study. The electric properties of the salt were studied using the impedance spectroscopy method. WB97XD/6-311++G(d,p) calculations were performed, and the quantum theory of atoms in molecules (QTAiM) approach and the Hirshfeld surface method were applied to analyze the hydrogen bond interaction. It was found that temperature influences the spectroscopic properties of pyrazolium salt, particularly the carbonyl and hydroxyl frequencies. The influence of water molecules, connected by three-center hydrogen bonds with co-planar tetrameters, on the formation of structural defects is also discussed in this report.

Recombinant Human Plasma Gelsolin Stimulates Phagocytosis while Diminishing Excessive Inflammatory Responses in Mice with Pseudomonas aeruginosa Sepsis.

Plasma gelsolin (pGSN) is a highly conserved abundant circulating protein, characterized by diverse immunomodulatory activities including macrophage activation and the ability to neutralize pro-inflammatory molecules produced by the host and pathogen. Using a murine model of Gram-negative sepsis initiated by the peritoneal instillation of Pseudomonas aeruginosa Xen 5, we observed a decrease in the tissue uptake of IRDye®800CW 2-deoxyglucose, an indicator of inflammation, and a decrease in bacterial growth from ascitic fluid in mice treated with intravenous recombinant human plasma gelsolin (pGSN) compared to the control vehicle. Pretreatment of the murine macrophage line RAW264.7 with pGSN, followed by addition of Pseudomonas aeruginosa Xen 5, resulted in a dose-dependent increase in the proportion of macrophages with internalized bacteria. This increased uptake was less pronounced when cells were pretreated with pGSN and then centrifuged to remove unbound pGSN before addition of bacteria to macrophages. These observations suggest that recombinant plasma gelsolin can modulate the inflammatory response while at the same time augmenting host antibacterial activity.

Investigation of spectroscopic and electrical properties of doped poly(pyrrole-3-carboxylic acid).

The spectroscopic and electrical properties of poly(pyrrole-3-carboxylic acid) doped with p-TSA- (p-toluenesulfonate) and AQS- (anthraquinone sulfonate) were investigated. The variation in electrical conductivity as a function of temperature shows that the systems have semiconductor-like electrical characteristics. The investigated polymers exhibit 3D conductivity and less than 0.6 eV energy gaps. The IR and Raman spectra show that the charge carriers are polarons and bipolarons. Doping the poly(pyrrole-3-carboxylic acid) increases the number of charge carriers. Electron paramagnetic resonance has shown that localized polarons and bipolarons are formed within these polymers.

Magnetic particles with polymeric shells bearing lithocholic and folic acid moieties: Nano-warriors to fight colon cancer.

In the study, we aimed to investigate the activity of nanoformulations containing 5-fluorouracil and polymer-magnetic hybrids bearing membrane-penetrating and ligand-receptor-recognizing agents against colorectal cancer cells. The formation and characterization of iron oxide particles covered with polymeric shells comprising lithocholic acid and folic acid moieties are presented. The efficiency of nanoformulations combined by the simple mixing of low doses of 5-fluorouracil with the obtained hybrids was demonstrated against DLD-1 and HT-29 colon cancer cells. The most pronounced cytotoxic potential against HT-29 cells was observed in the cases of particles based on block and randomly arranged copolymers functionalized by FA motifs with depletion of viable cells by approximately 50 % compared to control cells and cells treated by 5-FU applied in free form. In the case of the DLD-1 cell line, the percentage of viable DLD-1 cells decreased by about 30 to 40% after treatment with the block and randomly arranged copolymer decorated by FA-moiety, when compared to 5-FU at the free form and the untreated control. The induction of apoptosis associated with PS-translocation was determined to be the main mechanism of their cytotoxic effects. Moreover, the safety profiles of the nanoformulations were established through hemolysis assay and the analysis of the viability of human colorectal fibroblasts. It was indicated that all tested nanoparticles met the compatibility requirements at the in vitro level. It should be emphasized that in many cases, there was a significant improvement in the compatibility of hybrids with the FA motif compared to non-functionalized hybrids with the addition of 5-FU. These findings suggest that the presence of FA might modulate the toxicity of chemotherapeutic agents.

Lithocholic acid-based oligomers as drug delivery candidates targeting model of lipid raft.

This study presents a new approach to designing a lithocholic acid functionalized oligomer (OLithocholicAA-X) that can be used as a drug carrier with additional, beneficial activity. Namely, this novel oligomer can incorporate an anti-cancer drug due to the application of an effective backbone as its component (lithocholic acid) alone is known to have anticancer activity. The oligomer was synthesized and characterized in detail by nuclear magnetic resonance, attenuated total reflectance Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, thermal analysis, and mass spectrometry analysis. We selected lipid rafts as potential drug carrier-membrane binding sites. In this respect, we investigated the effects of OLithocholicAA-X on model lipid raft of normal and altered composition, containing an increased amount of cholesterol (Chol) or sphingomyelin (SM), using Langmuir monolayers and liposomes. The surface topography of the studied monolayers was additionally investigated by atomic force microscopy (AFM). The obtained results showed that the investigated oligomer has affinity for a system that mimics a normal lipid raft (SM:Chol 2:1). On the other hand, for systems with an excess of SM or Chol, thermodynamically unfavorable fluidization of the films occurs. Moreover, AFM topographies showed that the amount of SM determines the bioavailability of the oligomer, causing fragmentation of its lattice.

Composites containing resins and carbon nano-onions as efficient porous carbon materials for supercapacitors.

Herein, we report the functionalization of carbon nano-onions (CNOs) with the hydroxyaryl group and subsequent modifications with resins: resorcinol-formaldehyde using porogenic Pluronic F-127, resorcinol-formaldehyde-melamine, benzoxazine made of bisphenol A and triethylenetetramine, and calix[4]resorcinarene-derived using F-127. Following the direct carbonization, extensive physicochemical analysis was carried out, including Fourier transform infrared, Raman and X-ray photoelectron spectroscopy, scanning and transmission electron microscopy, and adsorption-desorption of N2. The addition of CNO to the materials significantly increases the total pore volume (up to 0.932 cm3 g-1 for carbonized resorcinol-formaldehyde resin and CNO (RF-CNO-C) and 1.242 cm3 g-1 for carbonized resorcinol-formaldehyde-melamine resin and CNO (RFM-CNO-C)), with mesopores dominating. However, the synthesized materials have poorly ordered domains with some structural disturbance; the RFM-CNO-C composite shows a more ordered structure with amorphous and semi-crystalline regions. Subsequently, cyclic voltammetry and galvanostatic charge-discharge method studied the electrochemical properties of all materials. The influence of resins' compositions, CNO content, and amount of N atoms in carbonaceous skeleton on the electrochemical performance was studied. In all cases, adding CNO to the material improves its electrochemical properties. The carbon material derived from CNO, resorcinol and melamine (RFM-CNO-C) showed the highest specific capacitance of 160 F g-1 at a current density of 2 A g-1, which is stable after 3000 cycles. The RFM-CNO-C electrode retains approximately 97% of its initial capacitive efficiency. The electrochemical performance of the RFM-CNO-C electrode results from the hierarchical porosity's stability and the presence of nitrogen atoms in the skeleton. This material is an optimal solution for supercapacitor devices.

Three-dimensional organization of pyrrolo[3,2-b]pyrrole-based triazine framework using nanostructural spherical carbon: enhancing electrochemical performance of materials for supercapacitors.

Covalent triazine-based frameworks have attracted much interest recently due to their high surface area and excellent thermal and electrochemical stabilities. This study shows that covalently immobilizing triazine-based structures on spherical carbon nanostructures results in the organization of micro- and mesopores in a three-dimensional manner. We selected the nitrile-functionalized pyrrolo[3,2-b]pyrrole unit to form triazine rings to construct a covalent organic framework. Combining spherical carbon nanostructures with the triazine framework produced a material with unique physicochemical properties, exhibiting the highest specific capacitance value of 638 F g-1 in aqueous acidic solutions. This phenomenon is attributed to many factors. The material exhibits a large surface area, a high content of micropores, a high content of graphitic N, and N-sites with basicity and semi-crystalline character. Thanks to the high structural organization and reproducibility, and remarkably high specific capacitance, these systems are promising materials for use in electrochemistry. For the first time, hybrid systems containing triazine-based frameworks and carbon nano-onions were used as electrodes for supercapacitors.

Assembly of Poly(vinylphosphonic acid)-Based Double Hydrophilic Block Copolymers by Gadolinium Ions for the Formation of Highly Stable MRI Contrast Agents.

Mixing double-hydrophilic block copolymers containing a poly(vinylphosphonic acid) block with gadolinium ions in water leads to the spontaneous formation of polymeric nanoparticles. With an average diameter near 20 nm, the nanoparticles are stable after dilution or change of pH and ionic strength. High magnetic relaxivities were measured in vitro, and in vivo magnetic resonance imaging on rats demonstrates the high potential of such polymeric assemblies.

Polymeric Network Hierarchically Organized on Carbon Nano-onions: Block Polymerization as a Tool for the Controlled Formation of Specific Pore Diameters.

The organization of specific pores in carbonaceous three-dimensional networks is crucial for efficient electrocatalytic processes and electrochemical performance. Therefore, the synthesis of porous materials with ordered and well-defined pores is required in this field. The incorporation of carbon nanostructures into polymers can create material structures that are more ordered in comparison to those of the pristine polymers. In this study we applied polymer-templated methods of carbon material preparation, in which outer blocks of the star copolymers form the carbon skeleton, while the core part is pore-forming. Well-defined 6-star-(poly(methyl acrylate)-b-poly(4-acetoxystyrene)) dendrimers were synthesized by reversible addition-fragmentation chain-transfer polymerization. They were then transformed into poly(4-vinylphenol) derivatives (namely 6-star-(poly(methyl acrylate)-b-poly(4-vinylphenol)), subjected to polycondensation with formaldehyde, and pyrolyzed at 800 °C. Cross-linking of phenolic groups provides a polymer network that does not depolymerize by pyrolysis, unlike poly(methyl acrylate) chains. The selected star polymers were attached to carbon nano-onions (CNOs) to improve the organization of the polymer chains. Herein, the physicochemical properties of CNO-polymer hybrids, including the textural and the electrochemical properties, were compared with those of the pristine pyrolyzed polymers obtained under analogous experimental conditions. For these purposes, we used several experimental and theoretical methods, such as infrared, Raman, and X-ray photoelectron spectroscopy, nitrogen adsorption/desorption measurements, scanning and transmission electron microscopy, and electrochemical studies, including cyclic voltammetry. All of the porous materials were evaluated for use as supercapacitors.

Doxorubicin delivery systems with an acetylacetone-based block in cholesterol-terminated copolymers: Diverse activity against estrogen-dependent and estrogen-independent breast cancer cells.

The study presents the synthesis of original cholesterol-terminated copolymers comprising acetylacetone-based (AcacI) and N-isopropylacrylamide (NIPAAm) units with a varied arrangement (block and random copolymers). The nanoprecipitation method was used to form empty and doxorubicin-loaded polymeric nanoparticles (PNPs) from these copolymers, which were further studied in terms of their physicochemical and biological properties. Unexpectedly, it was revealed that even empty PNPs are effective against breast cancer cells, specifically towards estrogen-dependent MCF-7 cell line. The anti-cancer efficacy was further improved when a low dose of doxorubicin was introduced to the tested systems. It was shown that the proposed carriers modulate doxorubicin (DOX) compatibility with representatives of normal cells, including immune cells, cardiomyocyte cells, and fibroblasts, and reduce side effects associated with standard chemotherapy. The use of these carriers might be a strategy leading to enhancement of DOX activity in cancer cells which develop resistance through decreased drug penetration or drug efflux.

Hydrolysable tannins change physicochemical parameters of lipid nano-vesicles and reduce DPPH radical - Experimental studies and quantum chemical analysis.

Tannins belong to plant secondary metabolites exhibiting a wide range of biological activity. One of the important aspects of the realization of the biological effects of tannins is the interaction with lipids of cell membranes. In this work we studied the interaction of two hydrolysable tannins: 1,2,3,4,6-penta-O-galloyl-ß-d-glucose (PGG) and 1,2-di-O-galloyl-4,6-valoneoyl-ß-d-glucose (T1) which had the same number of both aromatic rings (5) and hydroxyl groups (15) but differing in flexibility due to the presence of valoneoyl group in the T1 molecule with DMPC (dimyristoylphosphatidylcholine) lipid nano-vesicles (liposomes). Tannins-liposomes interactions were investigated using fluorescence spectroscopy, differential scanning calorimetry, laser Doppler velocimetry, dynamic light scattering and Fourier Transform Infra-Red spectroscopy. It was shown that more flexible PGG molecules stronger decreased the microviscosity of the liposomal membranes and increased the values of negative zeta potential in comparison with the more rigid T1. Both compounds diminished the phase transition temperature of DMPC membranes, interacted with liposomes via PO groups of head of phospholipids and their hydrophobic regions. These tannins neutralized DPPH free radicals with the stoichiometry of the reaction equal 1:1. The effects of the studied compounds on liposomes were discussed in relation to tannin quantum chemical parameters calculated by molecular modeling.

Effect of oil pomaces on thermal properties of model dough and gluten network studied by thermogravimetry and differential scanning calorimetry.

Thermal analyses were used to determine thermal properties and transitions in model dough and gluten network induced by five oil pomaces obtained from seeds of black seed, pumpkin, hemp, milk thistle and primrose. The model dough was supplemented with 3%, 6% and 9% of the pomaces. Analysis of TGA parameters of supplemented model dough and gluten showed that both objects were thermally stable. However, analysis of difference TGA thermograms indicated that samples supplemented with pomaces differ in thermal behaviour. The differences were confirmed by DSC results. In the case of model dough, supplementation caused appearance of two endothermic peaks at ca. 295 and 340 °C and significant increase in transition enthalpy. Modified gluten thermograms showed one exothermic peak at 280 °C which enthalpy changed slightly with increase in pomace content. The present results indicated that model dough is characterized by more ordered structure comparing to control and gluten samples.

Polymeric Drug Delivery Systems Bearing Cholesterol Moieties: A Review.

This review aims to provide an overview of polymers comprising cholesterol moiety/ies designed to be used in drug delivery. Over the last two decades, there have been many papers published in this field, which are summarized in this review. The primary focus of this article is on the methods of synthesis of polymers bearing cholesterol in the main chain or as side chains. The data related to the composition, molecular weight, and molecular weight distribution of polymers are presented. Moreover, other aspects, such as forms of carriers, types of encapsulated drugs, encapsulation efficiency and capacity, are also included.

Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells.

PURPOSE: Efficient intracellular delivery of a therapeutic compound is an important feature of smart drug delivery systems (SDDS). Modification of a carrier structure with a cell-penetrating ligand, ie, cholesterol moiety, is a strategy to improve cellular uptake. Cholesterol end-capped poly(N-isopropylacrylamide)s offer a promising foundation for the design of efficient thermoresponsive drug delivery systems. METHODS: A series of cholesterol end-capped poly(N-isopropylacrylamide)s (PNIPAAm) with number-average molar masses ranging from 3200 to 11000 g·mol-1 were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization from original xanthate-functionalized cholesterol and self-assembled into micelles. The physicochemical characteristics and cytotoxicity of cholesterol end-capped poly(N-isopropylacrylamide)s have been thoroughly investigated. RESULTS: Phase transition temperature dependence on the molecular weight and hydrophilic/hydrophobic ratio in the polymers were observed in water. Biological test results showed that the obtained materials, both in disordered and micellar form, are non-hemolytic, highly compatible with fibroblasts, and toxic to glioblastoma cells. It was found that the polymer termini dictates the mode of action of the system. CONCLUSION: The cholesteryl moiety acts as a cell-penetrating agent, which enables disruption of the plasma membrane and in effect leads to the restriction of the tumor growth. Cholesterol end-capped PNIPAAm showing in vitro anticancer efficacy can be developed not only as drug carriers but also as components of combined/synergistic therapy.

Flavonoids modulate liposomal membrane structure, regulate mitochondrial membrane permeability and prevent erythrocyte oxidative damage.

In the present work, we investigated the interaction of flavonoids (quercetin, naringenin and catechin) with cellular and artificial membranes. The flavonoids considerably inhibited membrane lipid peroxidation in rat erythrocytes treated with tert-butyl hydroperoxide (700 µM), and the IC50 values for prevention of this process were equal to 9.7 ± 0.8 µM, 8.8 ± 0.7 µM, and 37.8 ± 4.4 µM in the case of quercetin, catechin and naringenin, respectively, and slightly decreased glutathione oxidation. In isolated rat liver mitochondria, quercetin, catechin and naringenin (10-50 µM) dose-dependently increased the sensitivity to Ca2+ ions - induced mitochondrial permeability transition. Using the probes TMA-DPH and DPH we showed that quercetin rather than catechin and naringenin strongly decreased the microfluidity of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomal membrane bilayer at different depths. On the contrary, using the probe Laurdan we observed that naringenin transfer the bilayer to a more ordered state, whereas quercetin dose-dependently decreased the order of lipid molecule packing and increased hydration in the region of polar head groups. The incorporation of the flavonoids, quercetin and naringenin and not catechin, into the liposomes induced an increase in the zeta potential of the membrane and enlarged the area of the bilayer as well as lowered the temperature and the enthalpy of the membrane phase transition. The effects of the flavonoids were connected with modification of membrane fluidity, packing, stability, electrokinetic properties, size and permeability, prevention of oxidative stress, which depended on the nature of the flavonoid molecule and the nature of the membrane.