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The use of fluorinated contrast agents in magnetic resonance imaging (MRI) facilitates improved image quality due to the negligible amount of endogenous fluorine atoms in the body. In this work, we present a comprehensive study of the influence of the amphiphilic polymer structure and composition on its applicability as contrast agents in 19F MRI. Three series of novel fluorine-containing poly(2-oxazoline) copolymers and terpolymers, hydrophilic-fluorophilic, hydrophilic-lipophilic-fluorophilic, and hydrophilic-thermoresponsive-fluorophilic, with block and gradient distributions of the fluorinated units, were synthesized. It was discovered that the CF3 in the 2-(3,3,3-trifluoropropyl)-2-oxazoline (CF3EtOx) group activated the cationic chain end, leading to faster copolymerization kinetics, whereby spontaneous monomer gradients were formed with accelerated incorporation of 2-methyl-2-oxazoline or 2-n-propyl-2-oxazoline with a gradual change to the less-nucleophilic CF3EtOx monomer. The obtained amphiphilic copolymers and terpolymers form spherical or wormlike micelles in water, which was confirmed using transmission electron microscopy (TEM), while small-angle X-ray scattering (SAXS) revealed the core-shell or core-double-shell morphologies of these nanoparticles. The core and shell sizes obey the scaling laws for starlike micelles predicted by the scaling theory. Biocompatibility studies confirm that all copolymers obtained are noncytotoxic and, at the same time, exhibit high sensitivity during in vitro 19F MRI studies. The gradient copolymers provide the best 19F MRI signal-to-noise ratio in comparison with the analogue block copolymer structures, making them most promising as 19F MRI contrast agents.

A two-step synthetic approach via the combination of living cationic ring-opening (CROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization techniques was used to produce novel amphiphilic block copolymers based on the water-soluble poly(2-methyl-2-oxazoline) (PMeOx), which holds protein repelling properties, linked to the hydrophilic–hydrophobic pH-responsive block poly[2-(diisopropylamino)ethyl methacrylate] (PDPA). Hydrodynamic flow focusing nanoprecipitation microfluidics (MF) was further employed to manufacture block copolymer self-assemblies. Interestingly, although all the synthesized macromolecules contained higher amounts of the pH-responsive segment, the microfluidic approach allowed the manufacturing of core–shell micelles and polymersomes. The morphology seems to be driven by the overall molecular weight of the block copolymers rather than by the hydrophilic-to-hydrophobic weight ratio. Longer and shorter amphiphilic chains enabled the manufacturing of core–shell assemblies and polymeric vesicles, respectively. The use of PMeOx and PDPA blocks confers serum stability and pH-responsive behavior to the nanoparticles in a pH window which is particularly useful for tumour detection and therapy. The self-assembled nanostructures are non-toxic even at fairly high polymer concentrations. All these features therefore can be useful in the design of pH-triggered nanoplatforms of distinct morphologies towards a variety of biomedical applications, for instance, the loading and delivery of hydrophobic and hydrophilic therapeutics.

In situ1H 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.

The advances in polymer chemistry have allowed the preparation of biomedical polymers using human metabolites as monomers that can hold unique properties beyond the required biodegradability and biocompatibility. Herein, we demonstrate the use of endogenous human metabolites (succinic and dilinoleic acids) as monomeric building blocks to develop a new series of renewable resource-based biodegradable and biocompatible copolyesters. The novel copolyesters were characterized in detail employing several standard techniques, namely 1H NMR, 13C NMR, and FTIR spectroscopy and SEC, followed by an in-depth thermomechanical and surface characterization of their resulting thin films (DSC, TGA, DMTA, tensile tests, AFM, and contact angle measurements). Also, their anti-fungal biofilm properties were assessed via an anti-fungal biofilm assay and the biological properties were evaluated in vitro using relevant human-derived cells (human mesenchymal stem cells and normal human dermal fibroblasts). These novel highly biocompatible polymers are simple and cheap to prepare, and their synthesis can be easily scaled-up. They presented good mechanical, thermal and anti-fungal biofilm properties while also promoting cell attachment and proliferation, outperforming well-known polymers used for biomedical applications (e.g. PVC, PLGA, and PCL). Moreover, they induced morphological changes in the cells, which were dependent on the structural characteristics of the polymers. In addition, the obtained physicochemical and biological properties can be design-tuned by the synthesis of homo- and -copolymers through the selection of the diol moiety (ES, PS, or BS) and by the addition of a co-monomer, DLA. Consequently, the copolyesters presented herein have high application potential as renewable and cost-effective biopolymers for various biomedical applications.

Spikelets NMR spectra are very popular as they enable the shortening of experimental time and give the possibility to obtain required NMR parameters for nuclei with ultrawide NMR patterns. Unfortunately, these resulted ssNMR spectra cannot be fitted directly in common software. For this reason, we developed UWNMRSpectralShape (USS) software which transforms spikelets NMR patterns into single continuous lines. Subsequently, these reconstructed spectral envelopes of the (Q)CPMG spikelets patterns can be loaded into common NMR software and automatically fitted, independently of experimental settings. This allows the quadrupole and chemical shift parameters to be accurately determined. Moreover, it makes fitting of spikelets NMR spectra exact, fast and straightforward. Funding Agencies|Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [GA 19-05259S]; Visegrad Scholarship [52010892]

We hypothesize, that physical network between Laponite® nanoparticles and high molecular weight polyelectrolyte formed by mixing of Laponite® nanodispersion (containing multivalent phosphate dispersant) and polyelectrolyte solution is strongly influenced by the type and content of dispersant, which forms electric double layer (EDL) closely to the Laponite® edges. Thus, optimum dispersant concentration is necessary to overcome clay-clay interactions (excellent clay delamination), but should not be exceeded, what would result in the EDL compression and weakening of attractions forming clay-polyelectrolyte network. Thus, deeper investigation of Laponite® nanodispersions is highly demanded since it would enable to better design the self-assembled clay-polyelectrolyte hydrogels.To study clay interparticle interactions in the presence of various multivalent phosphates, complementary methods providing wide nanodispersion characterization have been applied: zeta potential measurement and SAXS technique (electrostatic interactions), oscillatory rheology (nanodispersion physical state) and NMR experiments (ion immobilization degree).It was found that multivalent phosphates induce and tune strength of clay-polyelectrolyte interactions forming hydrogel network in terms of varying EDL on the Laponite® edges. Moreover, phosphate dispersing efficiency depends on the molecular size, chemical structure, and valence of the anion; its potential as efficient dispersant for hydrogel preparation can be evaluated by estimation of anion charge density.

Herein we present a comprehensive study on the role of Bronsted-acidic imidazolium ionic liquids (ILs) and imidazolium salts promoting the reaction between carboxyl and epoxide groups in a controll...

Implementing Li metal anodes provides the potential of substantially boosting the energy density of current Li-ion battery technology. However, it suffers greatly from fast performance fading large...

Poly(itaconic acid) (PIA) was synthesized by persulfate initiated free-radical polymerization of ternary Deep Eutectic Solvents (DES) containing equimolar amounts of itaconic acid (IA) as hydrogen-bond donor, quaternary ammonium salt, namely choline chloride (CC) or tetraethylammonium chloride (TEAC) as hydrogen-bonds acceptors, and water as the initiator solvent. The syntheses were carried out at 65 °C for 2 h, and polymers produced were purified by dialysis and by treatment on strong cation exchange resin. The microstructures of the polymers were analysed using 1H, 13C and 1H–13C HSQC NMR spectroscopy. The unexpected methylene and methine groups resulting from decarboxylation and/or branching as well as choline ester moieties were detected as irregular structures in PIA synthesised in IA-TEAC and IA-CC DES, respectively.

Novel multiresponsive hybrid biocompatible systems of κ-carrageenan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline)s with unique combination of responsiveness to external stimuli were synthesized and studied. The polymer thermoresponsive behavior proved the existence of both lower and upper critical solution temperatures in aqueous milieu, forming gel at lower temperature, a solution at room temperature and cloudy nanophase-separated dispersion at elevated temperature. The limit temperatures can easily be adjusted by the polyoxazoline graft length and grafting density. Moreover, the polymer behavior is additionally dependent on the concentration of potassium ions. The polymers behave similarly as the original κ-carrageenan, and thus, the poly(2-alkyl-2-oxazoline) grafts do not decrease the ability of the κ-carrageenan to form the self-assembled structures. Molecular principles beyond this multistimuli-responsive behavior were elucidated with the use of dynamic light scattering, magnetic resonance and fluorescence measurements as well as atomic force microscopy. These polymers could be used in a wide range of biological applications demanding thermo- and potassium-responsiveness.

Natural antioxidants, such as epigallocatechin-3-gallate and related phenolic compounds from tea, enhance particle cell-interactions and cellular uptake. In this study, surface of superparamagnetic iron oxide nanoparticles prepared by co-precipitation of Fe chlorides was modified with silica, polyethylenimine, poly(ethylene glycol), and poly( l -lysine) to protect the iron oxide core from redox-reactions with phenols, enhance uptake by the cells, prevent the particle aggregation, or enable conjugation with several phenol-based antioxidants. To reveal the relation between the particle uptake and chemical structure of the phenolic antioxidants, five of them were selected, namely phenol, phloroglucinol, chlorogenic, gallic, and tannic acid. After incubation of the phenol-modified nanoparticles with U87MG human glioma cells, intracellular levels of the reactive oxygen species were reduced in a similar manner, as measured by flow cytometry. Colorimetric iron assay revealed a comparable level of cell-associated particles, which was mostly independent on the applied external magnetic field. The results suggest that the poly( l -lysine)-based coating is responsible for the antioxidant effects of the particles; the phenol- and poly( l -lysine)-coatings enable effective colloidal stability in aqueous media and enhance cellular internalization of the nanoparticles.

The study describes the synthesis, physicochemical properties, and biological evaluation of polymer therapeutics based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers intended for a tumor-targeted immuno-oncotherapy. Water-soluble linear and cholesterol-containing HPMA precursors were synthesized using controlled reversible addition&ndash, fragmentation chain transfer polymerization to reach molecular weight Mn about 2 &times, 104 g&middot, mol&minus, 1 and low dispersity. These linear or self-assembled micellar conjugates, containing immunomodulatory agent cucurbitacin-D (CuD) or the anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond, showed a hydrodynamic size of 10&ndash, 30 nm in aqueous solutions. The CuD-containing conjugates were stable in conditions mimicking blood. Importantly, a massive release of active CuD in buffer mimicking the acidic tumor environment was observed. In vitro, both the linear (LP-CuD) and the micellar (MP-CuD) conjugates carrying CuD showed cytostatic/cytotoxic activity against several cancer cell lines. In a murine metastatic and difficult-to-treat 4T1 mammary carcinoma, only LP-CuD showed an anticancer effect. Indeed, the co-treatment with Dox-containing micellar polymer conjugate and LP-CuD showed potentiation of the anticancer effect. The results indicate that the binding of CuD, characterized by prominent hydrophobic nature and low bioavailability, to the polymer carrier allows a safe and effective delivery. Therefore, the conjugate could serve as a potential component of immuno-oncotherapy schemes within the next preclinical evaluation.

Contains fulltext : 244600.pdf (Publisher’s version ) (Open Access) Anticancer drug delivery strategies are designed to take advantage of the differential chemical environment in solid tumors independently, or to high levels of reactive oxygen species (ROS) or to low pH, compared to healthy tissue. Here, the design and thorough characterization of two functionalizable "AND gate" multiresponsive (MR) block amphiphilic copolymers are reported, aimed to take full advantage of the coexistence of two chemical cues-ROS and low pH-present in the tumor microenvironment. The hydrophobic blocks contain masked pH-responsive side chains, which are exposed exclusively in response to ROS. Hence, the hydrophobic polymer side chains will undergo a charge shift in a very relevant pH window present in the extracellular milieu in most solid tumors (pH 5.6-7.2) after demasking by ROS. Doxorubicin (DOX)-loaded nanosized "AND gate" MR polymersomes (MRPs) are fabricated via microfluidic self-assembly. Chemical characterization reveals ROS-dependent pH sensitivity and accelerated DOX release under influence of both ROS and low pH. Treatment of tumor-bearing mice with DOX-loaded nonresponsive and "AND gate" MRPs dramatically decreases cardiac toxicity. The most optimal "AND gate" MRPs outperform free DOX in terms of tumor growth inhibition and survival, shedding light on chemical requirements for successful cancer nanomedicine.

A series of waterborne polycarbonate-based poly(urethane-urea) nanocomposite films were prepared and characterized. An isocyanate excess of 30 mol% with respect to the hydroxyl groups was used in the procedure, omitting the chain-extension step of the acetone process in the dispersion preparation. The individual steps of the synthesis of the poly(urethane-urea) matrix were followed by nuclear magnetic resonance (NMR) spectroscopy. The nanofillers (1 wt% in the final nanocomposite) differed in nature and shape. Starch, graphene oxide and nanocellulose were used as representatives of organic nanofillers, while halloysite, montmorillonite, nanosilica and hydroxyapatite were used as representatives of inorganic nanofillers. Moreover, the fillers differed in their shape and average particle size. The films were characterized by a set of methods to obtain the tensile, thermal and surface properties of the nanocomposites as well as the internal arrangement of the nanoparticles in the nanocomposite film. The degradation process was evaluated at 37 &deg, C in a H2O2 + CoCl2 solution.

The lack of cellular and tissue specificities in conventional chemotherapies along with the generation of a complex tumor microenvironment (TME) limits the dosage of active agents that reaches tumor sites, thereby resulting in ineffective responses and side effects. Therefore, the development of selective TME-responsive nanomedicines is of due relevance toward successful chemotherapies, albeit challenging. In this framework, we have synthesized novel, ready-to-use ROS-responsive amphiphilic block copolymers (BCs) with two different spacer chemistry designs to connect a hydrophobic boronic ester-based ROS sensor to the polymer backbone. Hydrodynamic flow focusing nanoprecipitation microfluidics (MF) was used in the preparation of well-defined ROS-responsive PSs; these were further characterized by a combination of techniques [

Herein, it is reported for the first time that when mixed with choline chloride, itaconic acid (IA), normally a low-reactive vinyl monomer, undergoes initiator-free radical polymerization under normal daylight. Furthermore, the process results in the formation of abnormally high-molecular-weight poly(itaconic acid) derivatives with Mw greater than ≈800 000 g mol-1 . Detailed 1D/2D NMR studies indicate that the polymers have two types of ionizable moieties, that is, anionic carboxylic and cationic choline ester groups in an average molar ratio of 12:1. Potentiometric titration shows polyampholyte behavior of the polymers. Tentative mechanistic studies reveal that the daylight-induced polymerization is initiated by species generated via interactions of near UV light with IA. However, EPR findings show that choline also participates in secondary radical reactions. The obtained polyampholytes are useful bio-based materials for fast and straightforward fabrication of polymer-clay nanocomposite hydrogels with excellent mechanical properties.

We describe a family of thermoresponsive hybrid biodegradable peptidoglycan-like polymers, β-glucan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline)s, in the context of their physical, chemical and biological properties. Four polymer samples, differing in the polyoxazoline graft length (500–5000 Da), were synthesized using β-glucan extracted from Auricularia auricula-judae, which is known for its anticancer and immunomodulatory activities. The thermoresponsive behaviour of the prepared polymers were thoroughly studied using dynamic light scattering, fluorescence and magnetic resonance measurements, demonstrating an easy adjustment of the cloud point temperature by the graft length. Moreover, all samples show nontoxicity in vitro. The assay of oxidative burst of the polymorphonuclears established that the polymer immunostimulatory properties are not significantly influenced by their graft length considering the same amount of β-glucan. Thus, we showed that the desired immunostimulatory properties are not decreased by the polyoxazoline grafting of β-glucan, even they are not influenced by the graft length of the polyoxazoline chains. Therefore, for the intended application the final graft length can be chosen considering the polymer thermoresponsive properties only, while not influencing their immunostimulatory properties.

Persulfate initiated free radical homopolymerization of itaconic acid in aqueous media has been investigated at 65 °C. The research was focused on the elucidation of the chemical structure of low-molecular-weight side products and itaconic oligomers separated from polymeric fraction by dialysis (cut-off of 1000 Da). Nuclear magnetic resonance (NMR) 1H, 13C, 1H–13C me-HSQC and 1H–13C HMBC experiments and direct infusion electrospray ionization mass spectrometry (ESI-MS) operated in the negative ion mode have been combined to investigate the low-molecular fraction. It was found that 2-hydroxyparaconic and itatartaric acid are the primary oxidation products formed during free radical polymerization of itaconic acid. Besides, ESI-MS analysis revealed sulfate, hydroxyl and lactone terminal groups resulted from disproportionation, combination and transfer processes. Kinetics studies using Raman spectrometry in initiator range of 0.07–0.32 mol/L and for monomer concentration between 1.32 and 2.63 mol/L indicated non-classical dependency both polymerization rate and initiator decomposition rate on monomer and initiator concentration.

Magnetic resonance imaging using fluorinated contrast agents (19F MRI) enables to achive highcontrast in images due to the negligible fluorine background in living tissues. In this pilot study, we developed new biocompatible, temperature-responsive, and easily synthesized polymeric nanogels containing a sufficient concentration of magnetically equivalent fluorine atoms for 19F MRI purposes. The structure of the nanogels is based on amphiphilic copolymers containing two blocks, a hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) or poly(2-methyl-2-oxazoline) (PMeOx) block, and a thermoresponsive poly[N(2,2difluoroethyl)acrylamide] (PDFEA) block. The thermoresponsive properties of the PDFEA block allow us to control the process of nanogel self-assembly upon its heating in an aqueous solution. Particle size depends on the copolymer composition, and the most promising copolymers with longer thermoresponsive blocks form nanogels of suitable size for angiogenesis imaging or the labeling of cells (appr...

Structural changes during temperature-induced phase transition in D2O solutions of poly(2-ethyl-2-oxazoline) (PEOx) and P(EOx-grad-2-methyl-2-oxazoline (MOx)) copolymers were investigated by 1H NMR methods in combination with dynamic light scattering. NMR spectra showed that in PEOx solutions on molecular level structures formed during gradual heating are preserved during subsequent cooling. Phase transition in solutions of P(EOx-grad-MOx) copolymers as revealed by NMR exists irrespective the solution is turbid or nonturbid at higher temperatures. In contrast to PEOx homopolymers it is very broad, virtually independent of the copolymer composition and molecular weight, and reversible with some hysteresis. Reduced intensities of cross-peaks in NOESY spectra of copolymer solutions at elevated temperatures are mainly due to the changed mobility of copolymer segments. In all investigated solutions two types of water, “free” and “bound” with long and very short spin–spin relaxation times T2, respectively, were detected in the transition region and above the transition. The existence of two T2 components shows that exchange between “bound” and “free” water is slow regarding T2 values.

A rapid and eco-friendly reversible addition-fragmentation chain transfer (RAFT) polymerization reaction of the N-(2-hydroxypropyl) methacrylamide (HPMA) monomer under microwave irradiation (MWI) was demonstrated. A systematic investigation to determine the optimal conditions for the polymerization, such as the reaction time, solvents, monomer stoichiometry and RAFT agents, was implemented. The polymerization kinetics were obtained using two different chain transfer agents (CTAs), namely, commercial 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid and synthesized 4-cyano-4-(((ethylthio)carbonothioyl)thio)pentanoic acid, in the presence of 4,4′-azobis(4-cyanovaleric acid) as the initiator in various solvents. The controlled living character of the RAFT polymerization under MWI conditions was demonstrated by the linear increase in the number-average molecular weight (Mn) with monomer conversion. Moreover, good agreement between the theoretical and experimental Mn values was verified with pseudo-first-order kinetic plots, with low dispersities (Đ ≤ 1.04) if a favorable solvent and/or CTA was chosen. In addition, the ability of MWI to facilitate copolymer formation was demonstrated by the preparation of relevant copolymers, such as poly(HPMA-b-bocAPMA), poly(HPMA-b-MABH) and poly(HPMA-b-PDPA). Altogether, these facile synthetic approaches can find applications for the synthesis of PHPMA-based homo- and copolymers that have already been clinically tested and serve as hydrophilic high-potential alternatives to polyethylene oxide.

Polymers 13(9), 1465 (1-14) (2021). doi:10.3390/polym13091465, Here, we report on the construction of biodegradable poly(ethylene oxide monomethyl ether) (MPEO)-b-poly(��-caprolactone) (PCL) nanoparticles (NPs) having acid-labile (acyclic ketal group) linkage at the block junction. In the presence of acidic pH, the nanoassemblies were destabilized as a consequence of cleaving this linkage. The amphiphilic MPEO-b-PCL diblock copolymer self-assembled in PBS solution into regular spherical NPs. The structure of self-assemble and disassemble NPs were characterized in detail by dynamic (DLS), static (SLS) light scattering, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). The key of the obtained NPs is using them in a paclitaxel (PTX) delivery system and study their in vitro cytostatic activity in a cancer cell model. The acid-labile ketal linker enabled the disassembly of the NPs in a buffer simulating an acidic environment in endosomal (pH ~5.0 to ~6.0) and lysosomal (pH ~4.0 to ~5.0) cell compartments resulting in the release of paclitaxel (PTX) and formation of neutral degradation products. The in vitro cytotoxicity studies showed that the activity of the drug-loaded NPs was increased compared to the free PTX. The ability of the NPs to release the drug at the endosomal pH with concomitant high cytotoxicity makes them suitable candidates as a drug delivery system for cancer therapy., Published by MDPI, Basel

A conceptually new class of probes was developed for detection of bacterial siderophores (BSPs), important determinants of virulence and pathogenicity, using 31P nuclear magnetic resonance (31P NMR). These probes are based on biodegradable nontoxic nanoparticles of calcium phytate (CaIP6), which possess measurable signal on 31P NMR spectra. The nanoparticles were doped with paramagnetic Fe3+ ions broadening the magnetic resonance signal of 31P. Therefore, the nanoparticles were not detectable by 31P NMR in the environment not containing BSPs, however, in the presence of BSPs, the Fe3+ ion is released from the nanoparticles, and the 31P NMR signal become detectable. In vitro demonstration of this Fe3+ release was performed with BSP deferoxamine (DFO), exhibiting a complete depletion of Fe3+ within 2 h for the nanoparticles containing 17.7 mol% Fe (III). The Fe3+ depletion was accompanied with a restoration of 31P NMR signal.

Temperature behavior of D 2 O solutions of thermoresponsive diblock poly(ethylene oxide) (PEO)- b -poly( N -isopropylacrylamide) (PNIPAm) copolymers and Y-shape triblock PEO- b -(PNIPAm) 2 copolymers was investigated and compared with the phase transition of the PNIPAm homopolymer by combination of NMR and ATR FTIR spectroscopy, DSC and model quantum-chemical calculations. It is shown that the phase transition and structures of PNIPAm component (forming micellar cores) are significantly affected not only by the presence of the PEO block but also by copolymer architecture. Both these factors affect energetics of the phase transition, influence of the polymer concentration and behavior of bound water at elevated temperatures. They also affect the degree of dehydration of PNIPAm segments (C O groups) at temperatures above the phase transition which is higher for block copolymers (especially for the diblock) in comparison with PNIPAm homopolymer. NOESY NMR spectra likewise revealed influence of the architecture of the block copolymer on its conformational behavior in the pretransition region.

Alginate gels are an outstanding biomaterial widely applicable in tissue engineering, medicine, and pharmacy for cell transplantation, wound healing and efficient bioactive agent delivery, respectively. This contribution provides new and comprehensive insight into the atomic-resolution structure and dynamics of polyvalent ion-cross-linked alginate gels in microbead formulations. By applying various advanced solid-state NMR (ssNMR) spectroscopy techniques, we verified the homogeneous distribution of the cross-linking ions in the alginate gels and the high degree of ion exchange. We also established that the two-component character of the alginate gels arises from the concentration fluctuations of residual water molecules that are preferentially localized along polymer chains containing abundant mannuronic acid (M) residues. These hydrated M-rich blocks tend to self-aggregate into subnanometer domains. The resulting coexistence of two types of alginate chains differing in segmental dynamics was revealed by ...

This work describes the solvent-free sol–gel synthesis of epoxy-functionalized silica-based precursors in the presence of 1-butyl-3-methylimidazolium-based ionic liquids (ILs) containing different anions: chloride (Cl–) and methanesulfonate (MeSO3–). The IL-driven sol–gel mechanisms were investigated in detail using experimental characterizations (29Si NMR and ATR FTIR spectroscopy) and a theoretical computational method based on density functional theory (DFT). We observed complex IL influence on both hydrolysis and condensation steps, involving especially H-bonding and Coulomb coupling stabilization of the process intermediates. The obtained IL–silica precursors and their further xerogels were widely characterized (rheology measurements, MALDI TOF, 29Si NMR, ATR FTIR, and DFT simulation), which allowed observation of their precise silica structures and established their most energetically favorable conformations. The detected silica structures were dependent on the IL type and varied from highly condens...

We have developed a biodegradable, biocompatible system for the delivery of the antituberculotic antibiotic rifampicin with a built-in drug release and nanoparticle degradation fluorescence sensor. Polymer nanoparticles based on poly(ethylene oxide) monomethyl ether- block -poly(e-caprolactone) were noncovalently loaded with rifampicin, a combination that, to best of our knowledge, was not previously described in the literature, which showed significant benefits. The nanoparticles contain a Forster resonance energy transfer (FRET) system that allows real-time assessment of drug release not only in vitro , but also in living macrophages where the mycobacteria typically reside as hard-to-kill intracellular parasites. The fluorophore also enables in situ monitoring of the enzymatic nanoparticle degradation in the macrophages. We show that the nanoparticles are efficiently taken up by macrophages, where they are very quickly associated with the lysosomal compartment. After drug release, the nanoparticles in the cmacrophages are enzymatically degraded, with half-life 88 ± 11 min.

Carbon nanospecies (CNPs) are of high interest in current research due to their many unique properties. They may be created by common processes, such as burning. Therefore, they can become potential contaminants and may have a negative impact on human health and the biosphere. Moreover, they may also catalyze protein misfolding and subsequent amyloid formation, which is extremely hard to treat. We investigated the influence of single-walled carbon nanotubes (SWNTs), fullerene (C60), carbon quantum dots (CDs) and nanodiamonds (NDs) on amyloid formation. This research utilized the hen egg-white lysozyme (HEWL) as a model system. Fibrils were detected by fluorescence of thioflavin-T (ThT) or Nile red (NR) and the results were confirmed by transmission electron microscopy (TEM). We have found that NDs promoted amyloid fibril formation at all concentrations. The highest concentration of C60 (250 μg ml−1) accelerated the process of fibrillation, while smaller concentrations (16 and 80 μg ml−1) prolonged the lag phase and were comparable to the control. SWNTs prolonged the lag phase of amyloid formation at all concentrations. CDs efficiently terminated the growth of amyloid fibrils. When we compared the amyloidogenicity of all four types of CNPs, the following trend was apparent: NDs > control > C60 > CDs > SWNTs.

Novel conjugates of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers tethered with chitooligosaccharidic epitopes of varying lengths were shown to be potent ligands of a model lectin, wheat germ agglutinin (WGA). The azide-functionalized oligosaccharidic epitopes were prepared by the action of Tyr470Asn mutant β-N-acetylhexosaminidase from Talaromyces flavus in a single reaction step and were conjugated to HPMA copolymer precursors in a defined pattern and density through Cu+-catalyzed azide–alkyne cycloaddition. The soluble, biocompatible, and structurally flexible synthetic glycopolymers were studied for their binding to WGA in a competitive enzyme-linked lectin assay (ELLA), and the kinetics of interaction were analyzed by surface plasmon resonance (SPR). To the best of our knowledge, this study presents the first HPMA copolymers derivatized with long oligosaccharides that demonstrate high affinity to a lectin target. The binding affinities in the low nanomolar and subnanomolar ranges place the prepared glycopolymers among the best WGA ligands reported to date. This study demonstrates the targeting potential of these glycopolymers for therapeutically relevant lectins.

A new reactive oxygen species (ROS)-sensitive, self-immolative biodegradable polyoxalate prodrug based on the anticancer chemotherapeutic hormone analog diethylstilbestrol was synthesized via one-pot step-growth polymerization. The nanoparticles prepared from this prodrug undergo self-immolative degradation releasing the chemotherapeutic drug in ROS-rich environments, e.g., in cancer cells. This new ROS self-immolative polyprodrug backbone eliminates the need for a linker between polymer chain and drug, resulting in a more specific drug release and minimized toxic side effects to non-ROS-producing cells as proven by in vitro experiments. The strategy enables re-utilization of a successful chemotherapeutic agent that has been clinically under-utilized due to dose-related side effects.

Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of alveolar macrophages. These cells avidly take up nanoparticles, even without the use of specific targeting ligands, making the use of nanotherapeutics ideal for the treatment of such infections. Methoxy poly(ethylene oxide)- block-poly(e-caprolactone) nanoparticles of several different polymer blocks' molecular weights and sizes (20-110 nm) were developed and critically compared as carriers for rifampicin, a cornerstone in tuberculosis therapy. The polymeric nanoparticles' uptake, consequent organelle targeting and intracellular degradation were shown to be highly dependent on the nanoparticles' physicochemical properties (the cell uptake half-lives 2.4-21 min, the degradation half-lives 51.6 min-ca. 20 h after the internalization). We show that the nanoparticles are efficiently taken up by macrophages and are able to effectively neutralize the persisting bacilli. Finally, we demonstrate, using a zebrafish model of tuberculosis, that the nanoparticles are well tolerated, have a curative effect, and are significantly more efficient compared to a free form of rifampicin. Hence, these findings demonstrate that this system shows great promise, both in vitro and in vivo, for the treatment of tuberculosis.