Pulmonary hypertension is a cardiovascular disease with a low survival rate. The protein galectin-3 (Gal-3) binding β-galactosides of cellular glycoproteins plays an important role in the onset and development of this disease. Carbohydrate-based drugs that target Gal-3 represent a new therapeutic strategy in the treatment of pulmonary hypertension. Here, we present the synthesis of novel hydrophilic glycopolymer inhibitors of Gal-3 based on a polyoxazoline chain decorated with carbohydrate ligands. Biolayer interferometry revealed a high binding affinity of these glycopolymers to Gal-3 in the subnanomolar range. In the cell cultures of cardiac fibroblasts and pulmonary artery smooth muscle cells, the most potent glycopolymer 18 (Lac-high) caused a decrease in the expression of markers of tissue remodeling in pulmonary hypertension. The glycopolymers were shown to penetrate into the cells. In a biodistribution and pharmacokinetics study in rats, the glycopolymers accumulated in heart and lung tissues, which are most affected by pulmonary hypertension.

• MeSH
• arteria pulmonalis účinky léků   metabolismus   MeSH
• biologické markery MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• galektin 3 * antagonisté a inhibitory   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• plicní hypertenze * farmakoterapie   metabolismus   MeSH
• polymery chemie   farmakologie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• galektin 3 * MeSH
• polymery MeSH

In situ 1H NMR characterization of copolymerization reactions of various 2-oxazoline monomers at different molar ratios offers detailed insight into the build-up and composition of the polymer chains. Various 2-oxazolines were copolymerized in one single solvent, butyronitrile, with 2-dec-9'-enyl-2-oxazoline, where the double bond allows for post-polymerization modification and can function as a crosslinking unit to form polymer networks. The types of the monomers and their molar ratios in the feed have a strong effect on the microstructure of the forming copolymer chains. Copolymers comprising 2-dec-9'-enyl-2-oxazoline and either 2-ethyl-, 2-isopropyl-, 2-butyl-, 2-heptyl, 2-nonyl- or 2-phenyl-2-oxazoline, show significant differences in sequential structure of copolymers ranging from block to gradient and random ordering of the monomer units. 1H NMR was found to be a powerful tool to uncover detailed oxazoline copolymerization kinetics and evolution of chain composition.

• Publikační typ
• časopisecké články MeSH

Nanoparticles (NPs) represent an emerging platform for diagnosis and treatment of various diseases such as cancer, where they can take advantage of enhanced permeability and retention (EPR) effect for solid tumor accumulation. To improve their colloidal stability, prolong their blood circulation time and avoid premature entrapment into reticuloendothelial system, coating with hydrophilic biocompatible polymers is often essential. Most studies, however, employ just one type of coating polymer. The main purpose of this study is to head-to-head compare biological behavior of three leading polymers commonly used as "stealth" coating materials for biocompatibilization of NPs poly(ethylene oxide), poly(2-ethyl-2-oxazoline) and poly[N-(2-hydroxypropyl)methacrylamide] in an in vivo animal solid tumor model. We used radiolabeled biodegradable hydroxyapatite NPs as a model nanoparticle core within this study and we anchored the polymers to the NPs core by hydroxybisphosphonate end groups. The general suitability of polymers for coating of NPs intended for solid tumor accumulation is that poly(2-ethyl-2-oxazoline) and poly(ethylene oxide) gave comparably similar very good results, while poly[N-(2-hydroxypropyl)methacrylamide] was significantly worse. We did not observe a strong effect of molecular weight of the coating polymers on tumor and organ accumulation, blood circulation time, biodistribution and biodegradation of the NPs.

• Klíčová slova
• animal model, hydroxyapatite, nanoparticles, poly(2-ethyl-2-oxazoline), poly(ethylene oxide), poly[N-(2-hydroxypropyl)methacrylamide], solid tumor,
• Publikační typ
• časopisecké články MeSH

The synthesis and characterization of an ABA triblock copolymer based on hydrophilic poly(2-methyl-2-oxazoline) (pMeOx) blocks A and a modestly hydrophobic poly(2-iso-butyl-2-oxazoline) (piBuOx) block B is described. Aqueous polymer solutions were prepared at different concentrations (1-20 wt %) and their thermogelling capability using visual observation was investigated at different temperatures ranging from 5 to 80 °C. As only a 20 wt % solution was found to undergo thermogelation, this concentration was investigated in more detail regarding its temperature-dependent viscoelastic profile utilizing various modes (strain or temperature sweep). The prepared hydrogels from this particular ABA triblock copolymer have interesting rheological and viscoelastic properties, such as reversible thermogelling and shear thinning, and may be used as bioink, which was supported by its very low cytotoxicity and initial printing experiments using the hydrogels. However, the soft character and low yield stress of the gels do not allow real 3D printing at this point.

• Klíčová slova
• amphiphilic block copolymer, cytocompatibility, poly(2-oxazoline), viscoelasticity, thermoresponsive hydrogel,
• Publikační typ
• časopisecké články MeSH