77 research outputs found

    Sugar decorated star-shaped (co)polymerswith resveratrol-based core – physicochemicaland biological properties

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    Star-shaped glycopolymers due to the attractive combination of the physicochemical, morphological, self-assembly properties along with biological activity have gained increased attention as innovative agents in novel cancer therapies. Unfortunately, the production of these highly desirable biomaterials remains a challenge in modern macromolecular chemistry. The main reason for that is the low polymerizability of ionic glycomonomers originated from their steric congestion and the occurrence of ionic interactions that generally negatively influence the polymerization progress and hinder controllable reaction pathway. In this work, the new ionic sugar monomer was (co)polymerized for the first time via Activator Generated by Electron Transfer Atom Transfer Radical Polymerization (AGET ATRP) using a three-arm resveratrol-based core to obtain star-like (co)polymers. The obtained products were examined in terms of their physicochemical properties and morphology. Aside from the synthesis of these new glycopolymers, also a thorough description of their thermal properties, ability to self-assembly, the formation of stable superstructures was studied in detail. It was found that examined (co)polymers did not show any heterogeneities and phase separation, while their variation of glass transition temperature (Tg) was strictly related to the change in the number of glycomonomer. Also, the stability and shapes of formed superstructures strictly depend on their composition and topology. Finally, we have shown that synthesized carbohydrate-based polymers revealed high antiproliferative activity against several cancer cell lines (i.e., breast, colon, glioma, and lung cancer). The cytotoxic activity was particularly observed for star-shaped polymers that were systematically enhanced with the growing concentration of amine moieties and molecular weight. The results presented herein suggest that synthesized star-shaped glyco(co)polymers are promising as drug or gene carriers in anticancer therapies or anti-tumor agents, depending on their cytotoxicity. Graphical abstrac

    Synthesis and applications of [60]fullerene nanoconjugate with 5- aminolevulinic acid and its glycoconjugate as drug delivery vehicles

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    The 5-aminolevulinic acid (5-ALA) prodrug is widely used in clinical applications, primarily for skin cancer treatments and to visualize brain tumors in neurosurgery. Unfortunately, its applications are limited by unfavorable pharmacological properties, especially low lipophilicity; therefore, efficient nanovehicles are needed. For this purpose, we synthesized and characterized two novel water-soluble fullerene nanomaterials containing 5-ALA and D-glucuronic acid components. Their physicochemical properties were investigated using NMR, XPS, ESI mass spectrometry, as well as TEM and SEM techniques. In addition, HPLC and fluorescence measurements were performed to evaluate the biological activity of the fullerene nanomaterials in 5-ALA delivery and photodynamic therapy (PDT); additional detection of selected mRNA targets was carried out using the qRT-PCR methodology. The cellular response to the [60]fullerene conjugates resulted in increased levels of ABCG2 and PEPT-1 genes, as determined by qRT-PCR analysis. Therefore, we designed a combination PDT approach based on two fullerene materials, C60-ALA and C60-ALA-GA, along with the ABCG2 inhibitor Ko143

    A Thiosemicarbazone Derivative as a Booster in Photodynamic Therapy—A Way to Improve the Therapeutic Effect

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    Photodynamic therapy is one of the most patient friendly and promising anticancer therapies. The active ingredient is irradiated protoporphyrin IX, which is produced in the body that transfers energy to the oxygen-triggering phototoxic reaction. This effect could be enhanced by using iron chelators, which inhibit the final step of heme biosynthesis, thereby increasing the protoporphyrin IX concentration. In the presented work, we studied thiosemicarbazone derivative, which is a universal enhancer of the phototoxic effect. We examined several genes that are involved in the transport of the heme substrates and heme itself. The results indicate that despite an elevated level of ABCG2, which is responsible for the PpIX efflux, its concentration in a cell is sufficient to trigger a photodynamic reaction. This effect was not observed for 5-ALA alone. The analyzed cell lines differed in the scale of the effect and a correlation with the PpIX accumulation was observed. Additionally, an increased activation of the iron transporter MFNR1 was also detected, which indicated that the regulation of iron transport is essential in PDT

    Effect of the complex-formation ability of thiosemicarbazones containing (aza)benzene or 3-nitro-1,8-naphthalimide unit towards Cu(II) and Fe(III) ions on their anticancer activity

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    We recently described a novel class of thiosemicarbazones (TSCs) with a high anticancer activity. Now, we expanded this compound library with a new class of TSCs with a 3-nitro-1,8-naphthalene unit. Thus, a series of novel TSC conjugates was obtained to determine the effect of its chemical structure on spectroscopic properties, metal complexing and biological activity. They were prepared in a microwave reactor, provided compounds with both a high yield and purity. Nuclear magnetic resonance (1H and 13C NMR, COSY, HMQC) and infrared spectroscopy were used to characterize them structurally. Additionally, DFT calculations were performed in order to obtain the optimized ground-state geometry. Physicochemical spectroscopic studies were conducted in different solvents and conditions to assess the effect of the substituent on the optical properties and metal complexing ability. The anticancer activity was tested on three cancer cell lines and then correlated with the spectroscopic results. Here, we show based on in vitro chelating studies, that anticancer activity is closely correlated with the Fe3+ and Cu2+ chelating ability of these compounds

    The effect of high-pressure on organocatalyzed ROP of γ-butyrolactone

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    In this paper, we report 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) supported high-pressure approach enforcing Ring-Opening Polymerization (ROP) of γ-butyrolactone (GBL), that due to unfavorable thermodynamics and low ring strain, is considered as a hardly polymerizable monomer. Application of Broadband Dielectric Spectroscopy (BDS) allowed us to find optimal thermodynamic conditions to perform well-controlled and notably fast polymerization (even within 1 h!), avoiding undesired crystallization process. It was shown that by varying pressure and temperature conditions, we could control molecular weight, dispersity of recovered macromolecules, as well as rate and efficiency of the reaction that are significantly altered with respect to the reference process carried out at ambient conditions. Experiments performed at respectively very low temperature T = 233 K and low/ moderate pressure (p = 75–250 MPa) and much higher temperatures (T = 248–268 K) and compressions (p = 1000 MPa) yielded poly(γ-butyrolactone) (PGBL) of tailored absolute molecular weight in moderate range Mn = 2.8–15.0 (up to 30.3) kg/mol and narrow/moderate dispersity ranging from Đ = 1.12–1.89. What is more, the implementation of MALDI-TOF, GPC and DSC analyses, clearly indicated that as i) the time of reaction gets longer, ii) the amount of catalyst increases, iii) the temperature lowers, the content of cyclic products in produced polymers grows. This phenomenon influences the rheological properties (viscosity), foil formation ability (films) and cell culture proliferation features of the recovered macromolecules. Presented results open a highly effective and repeatable route to produce PGBL via pressure-assisted ROP and indicate the possibility of tuning properties of this polymer by varying concentration of cycles or eventual block copolymerization with other biorelevant monomers to meet the expectations of the biotechnological industry

    Interactions of a Water-Soluble Glycofullerene with Glucose Transporter 1. Analysis of the Cellular Effects on a Pancreatic Tumor Model

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    In recent years, carbon nanomaterials have been intensively investigated for their possible applications in biomedical studies, especially as drug delivery vehicles. Several surface modifications can modulate the unique molecular structure of [60]fullerene derivatives, as well as their physicochemical properties. For this reason, covalent modifications that would enable a greater water solubilization of the fullerene buckyball have been rapidly investigated. The most exciting applications of fullerene nanomaterials are as drug delivery vectors, photosensitizers in photodynamic therapy (PDT), astransfection or MRI contrast agents, antimicrobials and antioxidants. From these perspectives, the glucose derivatives of [60]fullerene seem to be an interesting carbon nanomaterial for biological studies. It is well-known that cancer cells are characterized by an increased glucose uptake and it has also been previously reported that the glucose transporters (GLUTs) are overexpressed in several types of cancers, which make them attractive molecular targets for many drugs. This study explored the use of a highly water-soluble glycofullerene (called Sweet-C60) in pancreatic cancer studies. Here, we describe the PANC-1 cell proliferation, migration, metabolic activity and glycolysis rate after incubations with different concentrations of Sweet-C60. The final results did not show any influence of the Sweet-C60 on various cancer cellular events and glycolysis, suggesting that synthesized glycofullerene is a promising drug delivery vehicle for treating pancreatic cancer

    High pressure as a novel tool for the cationic ROP of γ-butyrolactone

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    In this study, we report the acid-catalyzed and high pressure assisted ring-opening polymerization (ROP) of g-butyrolactone (GBL). The use of a dually-catalyzed approach combining an external physical factor and internal catalyst (trifluoromethanesulfonic acid (TfOH) or p-toluenesulfonic acid (PTSA)) enforced ROP of GBL, which is considered as hardly polymerizable monomer still remaining a challenge for the modern polymer chemistry. The experiments performed at various thermodynamic conditions (T ¼ 278–323 K and p ¼ 700–1500 MPa) clearly showed that the high pressure supported polymerization process led to obtaining well-defined macromolecules of better parameters (Mn ¼ 2200–9700 g mol 1; Đ ¼ 1.05–1.46) than those previously reported. Furthermore, the parabolic-like dependence of both the molecular weight (MW) and the yield of obtained polymers on variation in temperature and pressure at either isobaric or isothermal conditions was also noticed, allowing the determination of optimal conditions for the polymerization process. However, most importantly, this strategy allowed to significantly reduce the reaction time (just 3 h at room temperature) and increase the yield of obtained polymers (up to 0.62 gPGBL/gGBL). Moreover, despite using a strongly acidic catalyst, synthesized polymers remained non-toxic and biocompatible, as proven by the cytotoxicity test we performed in further analysis. Additional investigation (including MALDI-TOF measurements) showed that the catalyst selection affected not only MW and yield but also the linear/cyclic form content in obtained macromolecules. These findings show the way to tune the properties of PGBL and obtain polymer suitable for application in the biomedical industry

    The effect of glycerin content in sodium alginate/poly(vinyl alcohol)- based hydrogels for wound dressing application

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    The impact of different amounts of glycerin, which was used in the system of sodium alginate/poly(vinyl alcohol) (SA/PVA) hydrogel materials on the properties, such as gel fraction, swelling ability, degradation in simulated body fluids, morphological analysis, and elongation tests were presented. The study shows a significant decrease in the gel fraction from 80.5 2.1% to 45.0 1.2% with the increase of glycerin content. The T5 values of the tested hydrogels were varied and range from 88.7 C to 161.5 C. The presence of glycerin in the matrices significantly decreased the thermal resistance, which was especially visible by T10 changes (273.9 to 163.5 C). The degradation tests indicate that most of the tested materials do not degrade throughout the incubation period and maintain a constant ion level after 7-day incubation. The swelling abilities in distilled water and phosphate buffer solution are approximately 200–300%. However, we noticed that these values decrease with the increase in glycerin content. All tested matrices are characterized by the maximum elongation rate at break in a range of 37.6–69.5%. The FT-IR analysis exhibits glycerin changes in hydrogel structures, which is associated with the cross-linking reaction. Additionally, cytotoxicity results indicate good adhesion properties and no toxicity towards normal human dermal fibroblasts

    Cytotoxicity of ionic liquids on normal human dermal fibroblasts in the context of their present and future applications

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    The skin is the part of the body that is the most exposed to toxic substances; therefore, the impact of chemicals on the skin should be thoroughly studied prior to their implementation in any industrial-scale application. Herein, we examined and analyzed the influence of the structure of both the cation and anion of 31 different ionic liquids (ILs) on their cytotoxicity against normal human dermal fibroblasts in the context of their present and future potential applications. We found that imidazolium-based ILs combined with dialkyl phosphate anions or with the ethyl sulfate anion are the least cytotoxic. Notably, 1,3-diethylimidazolium ethyl sulfate can be potentially used as a hydraulic fluid similar to the commercially available hydraulic medium based on 1-ethyl-3-methylimidazolium ethyl sulfate. Moreover, the dialkyl phosphate-based ILs are considered as an efficient solvent for the utilization of lignocellulose-based biomass and as an extractant in eco-friendly and cost-effective processes for the extraction of bioplastic. Pyrrolidinium-based and cyano-based ILs, often used as heat transfer media and base fluids for ionanofluids, were also identified herein as good candidates based on their relatively low toxicity compared to other ILs

    Bio-based nanofluids of extraordinary stability and enhanced thermal conductivity as sustainable green heat transfer media

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    Nanofluids (NFs) as a new generation of heat transfer media can be applied inter alia as engine coolants, in the microelectronic industry for the cooling of electronic components and systems, and in solar panels. In the present study, the extraordinarily, that is, more than 1 year, stable NFs composed of multi-walled carbon nanotubes (MWCNTs), biomass-derived 1,2- propanediol or 1,3-propanediol, and poly(N-vinylpyrrolidone) were created and studied. The thermal conductivity and density of NFs did not change over 8 months, and NFs did not sediment over 14 months. The real image of NFs determined using transmission electron cryo-microscopy allowed us to prove that the extraordinary stability and enhanced thermal conductivity were resulted by fully individualized MWCNTs in the continuous phase and MWCNTs stabilized in dispersions by shorter carbon nanoparticles and mostly homogenous poly(N-vinylpyrrolidone) coating. The maximum enhancement in thermal conductivity was 22 and 20% for NFs composed of 2 wt % MWCNTs in comparison with that of pure 1,2-propanediol and 1,3-propanediol, respectively. The improved thermal properties were accompanied by the practically Newtonian nature of all NFs. The cytotoxicity test on normal human dermal fibroblasts indicated that the use of diols diminished the toxicity of MWCNTs. Finally, the thermal conductivity and Prandtl number of bio-based NFsas compared with those of commercial heat transfer fluids DOWCAL 200 and DOWCAL Npredestine them as superb green heat transfer media in sustainable energy systems