Highly sulfated malto-oligomers, similar to heparin and heparan-sulfate, have good antiviral, antimetastatic, anti-inflammatory and cell growth inhibitory effects. Due to their broad biological activities and simple structure, sulfated malto-oligomer derivatives have a great therapeutic potential, therefore, the development of efficient synthesis methods for their production is of utmost importance. In this work, preparation of α-(1→4)-linked oligoglucosides containing a sulfonatomethyl moiety at position C-6 of each glucose unit was studied by different approaches. Malto-oligomeric sulfonic acid derivatives up to dodecasaccharides were prepared by polymerization using different protecting groups, and the composition of the product mixtures was analyzed by MALDI-MS methods and size-exclusion chromatography. Synthesis of lower oligomers was also accomplished by stepwise and block synthetic methods, and then the oligosaccharide products were persulfated. The antiviral, anti-inflammatory and cell growth inhibitory activity of the fully sulfated malto-oligosaccharide sulfonic acids were determined by in vitro tests. Four tested di- and trisaccharide sulfonic acids effectively inhibited the activation of the TNF-α-mediated inflammatory pathway without showing cytotoxicity.
Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible polymer-based biomaterials fulfill the requirements of these therapeutics because they enable to obtain polymer biomaterials with optimized blood circulation, pharmacokinetics, biodegradability, and renal excretion. Herein, we describe an adaptable polymerization platform employed for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterials, therapeutics, or theranostics. Four chain transfer agents (CTA) were designed and successfully synthesized for the reversible addition-fragmentation chain transfer polymerization, allowing the straightforward synthesis of hydrolytically biodegradable structures of block copolymers-based biomaterials. The controlled polymerization using the CTAs enables controlling the half-life of the hydrolytic degradation of polymer precursors in a wide range from 5 h to 21 days. Moreover, the antitumor drug pirarubicin (THP) was successfully conjugated to the polymer biomaterials via a pH-sensitive hydrazone bond for in vitro and in vivo experiments. Polymer conjugates demonstrated superior antitumor efficacy compared to basic linear polymer-based conjugates. Notably, the biodegradable systems, even though those with degradation in the order of hours were selected, increased the half-life of THP in the bloodstream almost two-fold. Indeed, the presented platform design enables the main chain-end specific attachment of targeting ligands or diagnostic molecules. The adaptable polymerization platform design allows tuning of the biodegradability rate, stimuli-sensitive drug bonding, and optimized pharmacokinetics to increase the therapy outcome and system targeting, thus allowing the preparation of targeted or theranostic polymer conjugates. STATEMENT OF SIGNIFICANCE: Biodegradable and biocompatible polymer-based biomaterials are recognized as potential future bioactive nanomedicines. To advance the development of such biomaterials, we developed polymerization platforms utilizing tailored chain transfer agents allowing the straightforward synthesis of hydrolytically degradable polymer biomaterials with tuned biodegradability from hours to several days. The platform allows for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterial serving as drug carriers or theranostics. The therapeutic potential was validated by preparation of polymer biomaterials containing pirarubicin, anticancer drug, bound via pH sensitive bond and by showing prolonged blood circulation and increased antitumor activity while keeping the drug side effects low. This work paves the way for future development of biodegradable polymer biomaterials with advanced properties in drug delivery.
Volumetric shrinkage (VS) of conventional, bulk-fill, and core build-up resin-based composites (RBCs) of various thickness (1-5 mm) was measured using the modified bonded-disk method with confocal laser scanning microscopy. Additionally, the bottom-to-top ratio of Vickers hardness (%VH) was measured. Conventional RBCs exhibited significantly higher VS than bulk-fill and core build-up RBCs (p<0.05). As specimen thickness increased, VS relative to volume (%VS) and difference in VS at each depth (VSdepth) decreased. For conventional RBCs, there was a significant drop in VSdepth between 1 mm and 2 mm (p<0.05), and another drop was observed between 3 mm and 4 mm (p<0.05) where %VH decreased below 90%. For bulk-fill and core build-up RBCs, VSdepth decreased significantly between 2 mm and 3 mm (p<0.05), but %VH exceeded 90% even in 5 mm deep cavities. These results indicated that post-curing contributed to lower shrinkage in deeper layers, and that conventional RBCs were not adequately polymerized at the depth of over 3 mm.
19F magnetic resonance imaging (MRI) using fluoropolymer tracers has recently emerged as a promising, non-invasive diagnostic tool in modern medicine. However, despite its potential, 19F MRI remains overlooked and underused due to the limited availability or unfavorable properties of fluorinated tracers. Herein, we report a straightforward synthetic route to highly fluorinated 19F MRI nanotracers via aqueous dispersion polymerization-induced self-assembly of a water-soluble fluorinated monomer. A polyethylene glycol-based macromolecular chain-transfer agent was extended by RAFT-mediated N-(2,2,2-trifluoroethyl)acrylamide (TFEAM) polymerization in water, providing fluorine-rich self-assembled nanoparticles in a single step. The resulting nanoparticles had different morphologies and sizes ranging from 60 to 220 nm. After optimizing their structure to maximize the magnetic relaxation of the fluorinated core, we obtained a strong 19F NMR/MRI signal in an aqueous environment. Their non-toxicity was confirmed on primary human dermal fibroblasts. Moreover, we visualized the nanoparticles by 19F MRI, both in vitro (in aqueous phantoms) and in vivo (after subcutaneous injection in mice), thus confirming their biomedical potential.
STATEMENT OF PROBLEM: The bonding of light-activated adhesives to root canal dentin with an additional touch-polymerization activator has been insufficiently examined. PURPOSE: The purpose of this in vitro study was to investigate the effect of touch-polymerization activators and extended light-irradiation time on the microtensile bond strength (μTBS) of light-activated adhesives. MATERIAL AND METHODS: Post cavities were prepared in 50 extracted mandibular premolars and bonded using Prime&Bond Universal (PBU); PBU+Self Cure Activator (SCA); Clearfil SE Bond 2 (SEB); SEB+Clearfil DC Activator (DCA); or Clearfil Universal Bond Quick ER (UBQ). After light-irradiation for 10 or 20 seconds, the post cavities were filled with dual-activated resin core materials. Eight beams were prepared per specimen and subjected to the μTBS test. The μTBS data were analyzed by using 3-way ANOVAs with the Bonferroni correction (α=.05). RESULTS: The 3-way ANOVAs indicated that the use of touch-polymerization activators (SCA and DCA) significantly increased the μTBS of PBU and SEB in both the coronal (P=.015) and apical (P=.001) regions. The extension of light-irradiation time to 20 seconds significantly improved their μTBS in the apical region (P<.001), but not in the coronal region (P=.09). Light-irradiation for 20 seconds increased the μTBS of UBQ significantly in the coronal region (P=.014). CONCLUSIONS: Touch-polymerization activators improved the bond strength of light-activated adhesives to root canal dentin, especially when combined with an extended light-irradiation time.
Profilin 1 is a crucial actin regulator, interacting with monomeric actin and several actin-binding proteins controlling actin polymerization. Recently, it has become evident that this profilin isoform associates with microtubules via formins and interferes with microtubule elongation at the cell periphery. Recruitment of microtubule-associated profilin upon extensive actin polymerizations, for example, at the cell edge, enhances microtubule growth, indicating that profilin contributes to the coordination of actin and microtubule organization. Here, we provide further evidence for the profilin-microtubule connection by demonstrating that it also functions in centrosomes where it impacts on microtubule nucleation.
- MeSH
- aktiny metabolismus MeSH
- Caco-2 buňky MeSH
- centrozom metabolismus MeSH
- forminy metabolismus MeSH
- genový knockout MeSH
- lidé MeSH
- melanom experimentální metabolismus patologie MeSH
- mikrofilamentové proteiny metabolismus MeSH
- mikrotubuly metabolismus MeSH
- myši MeSH
- nádory kůže metabolismus patologie MeSH
- polymerizace MeSH
- profiliny genetika metabolismus MeSH
- signální transdukce genetika MeSH
- transfekce MeSH
- tubulin metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The objective of the study was to investigate alkali lignin polymerization/depolymerization pathways in subcritical water (SW) without additives. Following a SW treatment at 200, 250, 275 and 300 °C, the products were subjected to a comprehensive suite of analyses addressing the product speciation and molecular weight (MW) distribution. The MW reduction (1.4 times) in the solid products following the SW treatment indicated a surprisingly reduced impact of cross-linking/repolymerization at 300 °C and lower temperatures. This was further confirmed by thermal carbon analysis (TCA) showing a reduction in pyrolytic charring after the SW treatment. The TD-Py gas chromatography analysis of the SW treated lignin indicated that the solid residue is less oxygenated than the initial lignin (23 vs. 29% as confirmed by elemental analysis). Thus, deoxygenation rather than re-polymerization appears to be the main process route in the absence of catalysts within the temperature range considered.
The effect of long-term water storage on the regional ultimate tensile strength (UTS), water sorption (Wsp) and water solubility (Wsl) of conventional and bulk-fill resin composites at various depths was investigated. Composite specimens light-cured from one side were sectioned into beams corresponding to different depths (1-5 mm) and stored in water for 24 h, 1 week, 1 month, 6 months or 1 year. UTS increased during the first week and then gradually decreased over time, especially in deeper regions. Bulk-fill composites initially exhibited similar UTS at all depths, whereas the UTS of conventional composites at 1 mm and 5 mm differed significantly at all time points. Wsp and Wsl increased with depth and storage time, markedly at 3-5 mm after 1 month for conventional composites and after 6 months for bulk-fill composites. The signs of degradation at depths beyond 3 mm suggested that even bulk-fill composites have suboptimal properties in layers more than 3 mm in thickness.
- MeSH
- pevnost v tahu MeSH
- polymerizace MeSH
- rozpustnost MeSH
- složené pryskyřice * MeSH
- testování materiálů MeSH
- voda * MeSH
- Publikační typ
- časopisecké články MeSH
Polydopamine (PDA), also known as synthetic melanin, is widely used as a biomimetic anchoring layer for the modification of various solid substrates. PDA is utilized for a wide range of biomedical, sensing and tribological applications, even though the polymer's precise covalent structure has not been completely revealed yet. Even more, it is not evident to which extent the chemical nature of the substrate, on which the layer is formed, influences and predetermines the covalent structure of resulting PDA. In this contribution, we have studied the growth of PDA using various surface-sensitive techniques such as spectroscopic ellipsometry, atomic force microscopy and X-ray photoelectron spectroscopy. We supplemented grazing angle attenuated total reflection FTIR spectroscopy with multivariate statistical analysis to further gain analytical power. We have particularly focused on the effects of polymerization time and substrate on the PDA structure. We found notable differences in the chemical composition of PDA formed on gold and on surfaces terminated with oxides/reactive hydroxides such as silicon and N-dopped-TiO2 in the early stages of the layer formation. At the later stages of layer formation, a merely unified chemical structure was observed independently on the type of substrate.
- MeSH
- indoly * MeSH
- polymerizace MeSH
- polymery * MeSH
- povrchové vlastnosti MeSH
- Publikační typ
- časopisecké články MeSH
Novel composite films combining biocompatible polysaccharides with conducting polyaniline (PANI) were prepared via the in-situ polymerization of aniline hydrochloride in the presence of sodium hyaluronate (SH) or chitosan (CH). The composite films possess very good cytocompatibility in terms of adhesion and proliferation of two lines of human induced pluripotent stem cells (hiPSC). Moreover, the cardiomyogenesis and even formation of beating clusters were successfully induced on the films. The proportion of formed cardiomyocytes demonstrated excellent properties of composites for tissue engineering of stimuli-responsive tissues. The testing also demonstrated antibacterial activity of the films against E. coli and PANI-SH was able to reduce bacterial growth from 2 × 105 to < 1 cfu cm-2. Physicochemical characterization revealed that the presence of polysaccharides did not notably influence conductivities of the composites being ∼1 and ∼2 S cm-1 for PANI-SH and PANI-CH respectively; however, in comparison with neat PANI, it modified their topography making the films smoother with mean surface roughness of 4 (PANI-SH) and 14 nm (PANI-CH). The combination of conductivity, antibacterial activity and mainly cytocompatibility with hiPSC opens wide application potential of these polysaccharide-based composites.
- MeSH
- aniliny chemie MeSH
- antibakteriální látky chemie farmakologie MeSH
- biokompatibilní materiály chemie farmakologie MeSH
- buněčná adheze účinky léků MeSH
- buněčné linie MeSH
- chitosan chemie MeSH
- elektrická vodivost MeSH
- Escherichia coli účinky léků MeSH
- indukované pluripotentní kmenové buňky účinky léků metabolismus MeSH
- kyselina hyaluronová chemie MeSH
- lidé MeSH
- nanokompozity chemie MeSH
- polymerizace MeSH
- povrchové vlastnosti MeSH
- proliferace buněk účinky léků MeSH
- Staphylococcus aureus účinky léků MeSH
- tkáňové inženýrství metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
