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Radiation resistance of cancer cells represents one of the major challenges in cancer treatment. The novel self-assembled fluoralkylated diselenide nanoparticles (fluorosomes) based on seleno-l-cystine (17FSe

We developed acid-functionalized glycogen conjugates as supramolecular carriers for efficient encapsulation and inhibition of a model cationic peptide melittin─the main component of honeybee venom. For this purpose, we synthesized and characterized a set of glycogens, functionalized to various degrees by several different acid groups. These conjugates encapsulate melittin up to a certain threshold amount, beyond which they precipitate. Computer simulations showed that sufficiently functionalized conjugates electrostatically attract melittin, resulting in its efficient encapsulation in a broad pH range around the physiological pH. Hemolytic assays confirmed in vitro that the effective inhibition of melittin's hemolytic activity occurs for highly functionalized samples, whereas no inhibition is observed when using low-functionalized conjugates. It can be concluded that functional glycogens are promising carriers for cationic molecular cargos or antidotes against animal venoms under conditions, in which suitable properties such as biodegradability and biocompatibility are crucial.

Gold nanoparticles (AuNPs) can be used in diagnostic and therapeutic applications. The development of facile and fast synthetic approaches is accordingly desirable towards ready-to-use biomedical materials. We report a practical one-pot method for the synthesis in aqueous media and room temperature of surface-decorated AuNPs with enhanced biological responses. The gold ions could be reduced using only polyethyleneimine (PEI) derivatives containing sugar and-or alkyl chains acting simultaneously as reducing and stabilizing agent, without the aid of any other mediator. The process is possibly potentialized by the presence of the amino groups in the polymer chains which further confer colloidal stability. The kinetics of AuNPs nucleation and growth depends on the chemical nature of the polymer chains. Particularly, the presence of lactose moieties conjugated to the PEI chains conducted to surface-decorated AuNPs with low cytotoxicity that are remarkably faster uptaken by HepG2 cells. These cells overexpress asialoglycoprotein (ASGP-R), a galactose receptor. These findings may kick off significant advances towards the practical and ready-to-use manufacturing of functionalized AuNPs towards cell-targeting since the methodology is applicable for a large variety of other ligands that can be conjugated to the same polymer chains.

A new generation biomass-based filler for natural rubber, ‘hydrochar’ (HC), was obtained by hydrothermal carbonization of hardwood waste (sawdust). It was intended as a potential partial replacement for the traditional carbon black (CB) filler. The HC particles were found (TEM) to be much larger (and less regular) than CB: 0.5–3 µm vs. 30–60 nm, but the specific surface areas were relatively close to each other (HC: 21.4 m2/g vs. CB: 77.8 m2/g), indicating a considerable porosity of HC. The carbon content of HC was 71%, up from 46% in sawdust feed. FTIR and 13C-NMR analyses indicated that HC preserved its organic character, but it strongly differs from both lignin and cellulose. Experimental rubber nanocomposites were prepared, in which the content of the combined fillers was set at 50 phr (31 wt.%), while the HC/CB ratios were varied between 40/10 and 0/50. Morphology investigations proved a fairly even distribution of HC and CB, as well as the disappearance of bubbles after vulcanization. Vulcanization rheology tests demonstrated that the HC filler does not hinder the process, but it significantly influences vulcanization chemistry, canceling scorch time on one hand and slowing down the reaction on the other. Generally, the results suggest that rubber composites in which 10–20 phr of CB are replaced by HC might be promising materials. The use of HC in the rubber industry would represent a high-tonnage application for hardwood waste.

A new method for poly (3, 4-ethylenedioxythiophene) (PEDOT) synthesis based on acid-assisted polymerization is proposed, and the optical and structural properties of the obtained material are explo...

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.

The paper describes the successful preparation of onion micelles by sequential combination of self-assembly of amphiphilic polyelectrolytes (PEs) in aqueous media and electrostatic coassembly of co...

Tuberculosis represents a major global health problem for which improved approaches are needed to shorten the course of treatment and to combat the emergence of resistant strains. The development of effective and safe nanobead-based interventions can be particularly relevant for increasing the concentrations of antitubercular agents within the infected site and reducing the concentrations in the general circulation, thereby avoiding off-target toxic effects. In this work, rifampicin, a first-line antitubercular agent, was encapsulated into biocompatible and biodegradable polyester-based nanoparticles. In a well-established BALB/c mouse model of pulmonary tuberculosis, the nanoparticles provided improved pharmacokinetics and pharmacodynamics. The nanoparticles were well tolerated and much more efficient than an equivalent amount of free rifampicin.

In this work, levofloxacin (LVX), a third-generation fluoroquinolone antibiotic, is encapsulated within amphiphilic polymeric nanoparticles of a chitosan-g-poly(methyl methacrylate) produced by self-assembly and physically stabilized by ionotropic crosslinking with sodium tripolyphosphate. Non-crosslinked nanoparticles display a size of 29 nm and a zeta-potential of +36 mV, while the crosslinked counterparts display 45 nm and +24 mV, respectively. The cell compatibility, uptake, and intracellular trafficking are characterized in the murine alveolar macrophage cell line MH-S and the human bronchial epithelial cell line BEAS-2B in vitro. Internalization events are detected after 10 min and the uptake is inhibited by several endocytosis inhibitors, indicating the involvement of complex endocytic pathways. In addition, the nanoparticles are detected in the lysosomal compartment. Then, the antibacterial efficacy of LVX-loaded nanoformulations (50% w/w drug content) is assessed in MH-S and BEAS-2B cells infected with Staphylococcus aureus and the bacterial burden is decreased by 49% and 46%, respectively. In contrast, free LVX leads to a decrease of 8% and 5%, respectively, in the same infected cell lines. Finally, intravenous injection to a zebrafish larval model shows that the nanoparticles accumulate in macrophages and endothelium and demonstrate the promise of these amphiphilic nanoparticles to target intracellular infections.

Natural rubber composites were reinforced by the co-fillers ‘hydrochar’ (HC), obtained by hydrothermal carbonization of hardwood sawdust and commercial carbon black (CB). The content of the combined fillers was kept constant while their ratio was varied. The aim was to test the suitability of HC as a partial filler in natural rubber. Due to its larger particle size and hence smaller specific surface area, large amounts of HC reduced the crosslinking density in the composites. On the other hand, due to its unsaturated organic character, HC was found to display interesting chemical effects: if it was used as the exclusive filler component, it displayed a very strong anti-oxidizing effect, which greatly stabilized the rubber composite against oxidative crosslinking (and hence embrittlement). HC also affected the vulcanization kinetics in different ways, depending on the HC/CB ratio. Composites with HC/CB ratios 20/30 and 10/40 displayed interesting chemical stabilization in combination with fairly good mechanical properties. The performed analyses included vulcanization kinetics, tensile properties, determination of density of permanent and reversible crosslinking in dry and swollen states, chemical stability tests including TGA, thermo-oxidative aging tests in air at 180 °C, simulated weathering in real use conditions (‘Florida test’), and thermo-mechanical analyses of degraded samples. Generally, the results indicate that HC could be a promising filler material due to its specific reactivity.

A new type of hydrophilic, biocompatible, and biodegradable polypeptide nanogel depots loaded with natural serine protease inhibitor α1-antitrypsin (AAT) was applied for inhibition of inflammatory mediator trypsin. Further, poly[N5-(2-hydroxyethyl)-L-glutamine-ran-N5-propargyl-L-glutamine-ran-N5-(6-aminohexyl)-L-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-L-glutamine] (PHEG-Tyr) and Nα-L-Lysine-grafted α,β-poly[(2-propyne)-D,L-aspartamide-ran-(2-hydroxyethyl)-DL-aspartamide-ran-(2-(4-hydroxyphenyl)ethyl)-DL-aspartamide] (Nα-Lys-NG) nanogels were prepared by HRP/H2O2-mediated crosslinking in inverse miniemulsions with pH and temperature-stimuli responsive behavior confirmed by dynamic light scattering and zeta potential measurements. The loading capacity of PHEG-Tyr and Nα-Lys-NG nanogels and their release profiles were firstly optimized with bovine serum albumin (BSA) and then used for loading and release of AAT. PHEG-Tyr and Nα-Lys-NG nanogels showed different loading capacities for AAT with the maximum (20 %) achieved with Nα-Lys-NG nanogel. In both cases, the nanogels depots demonstrated a burst release of AAT during 6 h, which could be favorable for quick inhibition of trypsin. A consequent pilot in vitro inhibition study revealed that both PHEG-Tyr and Nα-Lys-NG nanogels loaded with AAT successfully inhibited the enzymatic activity of trypsin. Furthermore, the inhibitory efficiency of the AAT-loaded nanogels was higher than that of AAT itself, indicating that the negatively charged polypeptide nanogels enhance the inhibitory function of AAT loaded in the nanogel depots.

Novel stiff, tough, highly transparent and ultra-extensible self-assembled nanocomposite elastomers based on poly(2-methoxyethylacrylate) (polyMEA) were synthesized. The materials are physically crosslinked by small in-situ-formed silica nanospheres, sized 3–5 nm, which proved to be a very efficient macro-crosslinker in the self-assembled network architecture. Very high values of yield stress (2.3 MPa), tensile strength (3.0 MPa), and modulus (typically 10 MPa), were achieved in combination with ultra-extensibility: the stiffest sample was breaking at 1610% of elongation. Related nanocomposites doubly filled with nano-silica and clay nano-platelets were also prepared, which displayed interesting synergy effects of the fillers at some compositions. All the nanocomposites exhibit ‘plasto-elastic’ tensile behaviour in the ‘as prepared’ state: they display considerable energy absorption (and also ‘necking’ like plastics), but at the same time a large but not complete (50%) retraction of deformation. However, after the first large tensile deformation, the materials irreversibly switch to ‘real elastomeric’ tensile behaviour (with some creep). The initial ‘plasto-elastic’ stretching thus causes an internal rearrangement. The studied materials, which additionally are valuable due to their high transparency, could be of application interest as advanced structural materials in soft robotics, in implant technology, or in regenerative medicine. The presented study focuses on structure-property relationships, and on their effects on physical properties, especially on the complex tensile, elastic and viscoelastic behaviour of the polyMEA nanocomposites.

A modern scanning electron microscope equipped with a pixelated detector of transmitted electrons can record a four-dimensional (4D) dataset containing a two-dimensional (2D) array of 2D nanobeam electron diffraction patterns; this is known as a four-dimensional scanning transmission electron microscopy (4D-STEM). In this work, we introduce a new version of our method called 4D-STEM/PNBD (powder nanobeam diffraction), which yields high-resolution powder diffractograms, whose quality is fully comparable to standard TEM/SAED (selected-area electron diffraction) patterns. Our method converts a complex 4D-STEM dataset measured on a nanocrystalline material to a single 2D powder electron diffractogram, which is easy to process with standard software. The original version of 4D-STEM/PNBD method, which suffered from low resolution, was improved in three important areas: (i) an optimized data collection protocol enables the experimental determination of the point spread function (PSF) of the primary electron beam, (ii) an improved data processing combines an entropy-based filtering of the whole dataset with a PSF-deconvolution of the individual 2D diffractograms and (iii) completely re-written software automates all calculations and requires just a minimal user input. The new method was applied to Au, TbF3 and TiO2 nanocrystals and the resolution of the 4D-STEM/PNBD diffractograms was even slightly better than that of TEM/SAED.

This chapter is devoted to the tailored synthesis and study of the properties of novel surface-active polymeric drug carriers containing side chains of PEG and other, including polyelectrolyte, chains for waterborne delivery systems. The strategy of synthesis of PEG-containing polymeric carriers via reactions of radical polymerization and further polymer-analogous transformations involving epoxide (so called “grafting to”) and peroxide ("grafting from") fragments of epoxide-containing polyperoxides of various composition and fine structure were developed and studied. The dependence of PEG grafting degree on the length of the blocks of GMA links in the backbone was shown. Water-soluble surfactants combining grafted side PEG and anionic polyelectrolyte chains were synthesized using polymerization initiated by the comb-like PEG-containing macro-initiator with side peroxide groups. An another promising way of “grafting through” synthesis of the comb-like polymeric drug carriers with side PEG chains via controlled polymerization of PEG methacrylate macromers in the presence of functional chain transfer agents was developed. The molecular weight characteristics, functionality, and surface activity of the developed polymers were studied using SEC and GPC techniques, FT-IR, NMR spectroscopy, and elementary analysis. The binding of water-soluble and water-insoluble anticancer drugs with PEGylated carriers via combination of different mechanisms was studied by using luminescent, RAMAN, UV-spectroscopy, and surface tension measurement techniques. Stable waterborne drug delivery systems based on the polymeric micelles loaded with water-soluble and water-insoluble drugs were developed and studied using SAXS, TEM, SEM, and DLS methods. The developed PEG-containing comb-like polymeric carriers and derived drug delivery systems were shown to be nontoxic in vitro (cell cultures) and in vivo (laboratory mice and rats). Their use enhances drug delivery to tumor cells, reduces the effective drug therapeutic dose, and offers a possibility to circumvent acquired resistance of tumor cells to drug action.

We herein demonstrate the outstanding protein-repelling characteristic of star-like micelles and polymersomes manufactured from amphiphilic block copolymers made by poly(butylene oxide) (PBO) hydrophobic segments and polyglycidol (PGL) hydrophilic outer shells. Although positively charged proteins (herein modeled by lysozyme) may adsorb onto the surface of micelles and polymersomes where the assemblies are stabilized by short PGL chains (degree of polymerization smaller than 15), the protein adsorption vanishes when the degree of polymerization of the hydrophilic segment (PGL) is higher than ∼20, regardless the morphology. This has been probed by using three different model proteins which are remarkably different concerning molecular weight, size, and zeta potential (bovine serum albumin (BSA), lysozyme, and immunoglobulin G (IgG)). Indeed, the adsorption of the most abundant plasma protein (herein modeled as BSA) is circumvented even by using very short PGL shells due to the highly negative zeta potential of the produced assemblies which presumably promote protein-nanoparticle electrostatic repulsion. The negative zeta potential, on the other hand, enables lysozyme adsorption, and the phenomenon is governed by electrostatic forces as evidenced by isothermal titration calorimetry. Nevertheless, the protein coating can be circumvented by slightly increasing the degree of polymerization of the hydrophilic segment. Notably, the PGL length required to circumvent protein fouling is significantly smaller than the one required for PEO. This feature and the safety concerns regarding the synthetic procedures on the preparation of poly(ethylene oxide)-based amphiphilic copolymers might make polyglycidol a promising alternative toward the production of nonfouling spherical particles.

The paper is focused on investigation of layered double hydroxides (LDH) functionalized with ionic liquid (IL) as novel catalytic/initiating system for ring opening polymerization (ROP) of e-caprolactone. Firstly, the Ca2+/Al3+ LDH nanoparticles were synthesized via a co-precipitation method followed by the anion exchange using phosphonium IL with decanoate anions producing the modified LDH with interlayered IL-anions. Then, the progress of microwave-assisted polymerization in the presence of the modified LDH was studied showing the anionic mechanism of ROP initiated by the water molecules, which were adsorbed on the LDH surface and intercalated in the LDH galleries. The whole polymerization was significantly accelerated by microwave energy, which induced molecular rotations of the intercalated IL-anions leading to LDH delamination and exfoliation into individual nanosheets, which made the catalytic sites (IL-anions) easily accessible for the eCL molecules. The kinetics of microwave-assisted ROP thus showed a 4.6-fold increase of the reaction rate compared to the polymerization performed under conventional heating. Activation enthalpy and entropy were calculated for the microwave-assisted polymerizations initiated by the modified LDH. The use of microwave-active catalytic-initiating LDH nanoparticles enables to synthesize the organometallic catalyst-free PCL or, at higher LDH loadings, the highly-exfoliated PCL/LDH nanocomposites, which are highly desirable for e.g. packaging materials.

This work studies the influence of dip-coating parameters on self-assembly in ultra-thin films of asymmetric polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) copolymers from a 1-chloropentane solution using a combination of several experimental techniques. Small-Angle X-ray Scattering, Atomic Force Microscopy, Grazing Incidence Small Angle X-ray Scattering and Transmission Electron Microscopy were used to characterize the fabricated films. We have shown a facile fabrication route to smooth films with a wide range of thicknesses. Arranged domains of P4VP oriented perpendicularly to the substrate were observed. The domain sizes and spacing varied in the range from 13 up to 35 nm and from 39 to 115 nm, respectively.

In this work, we synthesized and characterized the self-assembly behavior of a chitosan-poly(methyl methacrylate) graft copolymer and the properties of the formed nanoparticles by static and dynamic light scattering, small-angle neutron scattering, and transmission electron microscopy. Overall, our results indicate that the hydrophobization of the chitosan side-chain with PMMA leads to a complex array of small unimolecular and/or small-aggregation number "building blocks" that further self-assemble into larger amphiphilic nanoparticles.

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

We introduce a novel scanning electron microscopy (SEM) method which yields powder electron diffraction patterns. The only requirement is that the SEM microscope must be equipped with a pixelated detector of transmitted electrons. The pixelated detectors for SEM have been commercialized recently. They can be used routinely to collect a high number of electron diffraction patterns from individual nanocrystals and/or locations (this is called four-dimensional scanning transmission electron microscopy (4D-STEM), as we obtain two-dimensional (2D) information for each pixel of the 2D scanning array). Nevertheless, the individual 4D-STEM diffractograms are difficult to analyze due to the random orientation of nanocrystalline material. In our method, all individual diffractograms (showing randomly oriented diffraction spots from a few nanocrystals) are combined into one composite diffraction pattern (showing diffraction rings typical of polycrystalline/powder materials). The final powder diffraction pattern can be analyzed by means of standard programs for TEM/SAED (Selected-Area Electron Diffraction). We called our new method 4D-STEM/PNBD (Powder NanoBeam Diffraction) and applied it to three different systems: Au nano-islands (well diffracting nanocrystals with size ~20 nm), small TbF3 nanocrystals (size &lt, 5 nm), and large NaYF4 nanocrystals (size &gt, 100 nm). In all three cases, the STEM/PNBD results were comparable to those obtained from TEM/SAED. Therefore, the 4D-STEM/PNBD method enables fast and simple analysis of nanocrystalline materials, which opens quite new possibilities in the field of SEM.

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.

We report the controlled synthesis of polymer-stabilized silver nanoparticles (AgNPs) by using microfluidic devices. The microfluidic-based method enabled the preparation of sub-50 nm AgNPs which are much more homogenous compared to those produced in batch reactors where the control over flow and mixing conditions was not performed. The concentration of the silver precursor (silver nitrate - AgNO₃) can be tuned to reach smaller or larger nanoparticles, although within a fairly narrow range. Regardless of the polymeric shell, the reducing agent concentration influences the size and polydispersity of the manufactured silver colloids, and relatively lower amounts allow for the manufacturing of more homogeneous nanoparticles. Notably, the use of the block copolymer PEO-b-P2VP as stabilizing agent leads to larger nanoparticles (23–51 nm) compared to those stabilized by PVP (7–14 nm) as possibly linked to different arrangements of the polymer chains at the interface between the precursor solutions. The produced AgNPs are highly uniform, with size distribution width influenced by the polymer concentration (FWHM < 100 nm were determined at higher concentrations), although this variable does not have a distinguished effect on the final size of the manufactured colloids. Overall, we provide relevant new knowledge within the framework of polymer-stabilized AgNPs since a variety of other polymer chains can be probed, possibly with different outcomes regarding the final particle size. The reported findings can thus guide to significant advances towards the manufacturing of highly homogeneous polymer-coated metallic colloids, particularly when a target size is required.

Horseradish peroxidase (HRP)/H2O2-mediated crosslinking of polypeptides in inverse miniemulsion is a promising approach for the development of next-generation biocompatible and biodegradable nanogels. Herein, we present a fundamental investigation of the effects of three surfactants and their different concentrations on the (HRP)/H2O2-mediated nanogelation of poly[N5-(2-hydroxyethyl)- l -glutamine-ran-N5-propargyl- l -glutamine-ran-N5-(6-aminohexyl)- l -glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)- l -glutamine] (PHEG-Tyr) in inverse miniemulsion. The surfactants sorbitan monooleate (SPAN 80), polyoxyethylenesorbitan trioleate (TWEEN 85), and dioctyl sulfosuccinate sodium salt (AOT) were selected and their influence on the nanogel size, size distribution, and morphology was evaluated. The most effective nanogelation stabilization was achieved with 20 wt% nonionic surfactant SPAN 80. The diameter of the hydrogel nanoparticles was 230 nm (dynamic light scattering, DLS) and was confirmed also by nanoparticle tracking analysis (NTA) which showed the diameters ranging from 200 to 300 nm. Microscopy and image analyses showed that the nanogel in the dry state was spherical in shape and had number-average diameter Dn = 26 nm and dispersity Ð = 1.91. In the frozen-hydrated state, the nanogel appeared porous and was larger in size with Dn = 182 nm and Ð = 1.52. Our results indicated that the nanogelation of the polymer precursor required a higher concentration of surfactant than classical inverse miniemulsion polymerization to ensure effective stabilization. The developed polypeptide nanogel was radiolabeled with 125I, and in vivo biodistribution and blood clearance evaluations were performed. We found that the 125I-labeled nanogel was well-biodistributed in the bloodstream, cleared from mouse blood during 48 h by renal and hepatic pathways and did not provoke any sign of toxic effects.

Colloidal-chemical characteristics of block/branched cationic and non-ionic polyamphiphiles containing poly(fluorine-alkyl methacrylate) (poly(FMA)) block and their intermolecular complexes with biopolymers were studied. The dependences of their surface activity and micelle size on the length of hydrophobic and hydrophilic blocks, as well as the length of side fluorine-alkyl branches were established. Poly(FMA)-block-poly(DMAEMA) was used for formation of interpolyelectrolyte complexes with plasmid DNA (pDNA) via their electrostatic interaction. Novel non-viral polyplexes were tested as gene delivery systems for mammalian cells. The results of DLS, TEM and MALDI-ToF studies demonstrated disaggregation of lysozyme (LYZ) aggregates in the presence of poly(FMA)-block-poly(NVP) and formation of the polyamphiphile…LYS complex possessing antibacterial action.

One-pot synthesis of gradient copolymers by statistical copolymerization represents an elegant route to amphiphilic copolymers as a basis for micellar systems. Herein, we propose a robust strategy to control the monomer distribution along the gradient copolymer chain by appropriate selection of the polymerization solvent. The gradient formation was investigated for copolymerizations of the hydrophilic 2-methyl-2-oxazoline (MeOx) and the hydrophobic 2-phenyl-2-oxazoline (PhOx) using sulfolane and acetonitrile as the polymerization solvents revealing a striking difference. In sulfolane, a quasi-block (CP2) like character was observed, whereas acetonitrile led to a more gradient-like (CP3) copolymer. The monomer distribution was found to have an impact on the micellization behavior of both amphiphilic copolymers, which was also compared with the analogous block copolymer (CP1). CP1 led to the formation of the smallest micelles, followed by a somewhat larger structure formed by CP2, while CP3 self-assembles into significantly larger nanoparticles. These findings open up a route to new amphiphilic copolymer systems with precisely fine-tuned architecture.

Clustered regularly interspaced short palindromic repeats-associated protein (CRISPR/Cas9) system has become a revolutionary tool for gene editing. Since viral delivery systems have significant side effects, and naked DNA delivery is not an option, the nontoxic, non-viral delivery of CRISPR/Cas9 components would significantly improve future therapeutic delivery. In this study, we aim at characterizing nanoparticles to deliver plasmid DNA encoding for the CRISPR-Cas system in eukaryotic cells in vitro. CRISPR/Cas9 complexed polyethylenimine (PEI) magnetic nanoparticles (MNPs) were generated. We used a stable HEK293 cell line expressing the traffic light reporter (TLR-3) system to evaluate efficient homology- directed repair (HDR) and non-homologous end joining (NHEJ) events following transfection with NPs. MNPs have been synthesized by co-precipitation with the average particle size around 20 nm in diameter. The dynamic light scattering and zeta potential measurements showed that NPs exhibited narrow size distribution and sufficient colloidal stability. Genome editing events were as efficient as compared to standard lipofectamine transfection. Our approach tested non-viral delivery of CRISPR/Cas9 and DNA template to perform HDR and NHEJ in the same assay. We demonstrated that PEI-MNPs is a promising delivery system for plasmids encoding CRISPR/Cas9 and template DNA and thus can improve safety and utility of gene editing.

HDPE-based nanocomposite fibers have been extruded from a melt and drawn up to draw ratio DR = 8. Two kinds of carbon nanodiscs (original ones and those exposed to additional annealing) have been used as fillers. Obtained nanocomposite fibers have been investigated with the help of different experimental methods: rheology, SEM and WAXS. It has been demonstrated that the annealed carbon nanodiscs possess a nucleation ability that finally leads to strong transformation of the material morphology.

Among external stimuli used to trigger release of a drug from a polymeric carrier, ultrasound has gained increasing attention due to its non-invasive nature, safety and low cost. Despite this attention, there is only limited knowledge about how materials available for the preparation of drug carriers respond to ultrasound. This study investigates the effect of ultrasound on the release of a hydrophobic drug, dexamethasone, from poly(2-oxazoline)-based micelles. Spontaneous and ultrasound-mediated release of dexamethasone from five types of micelles made of poly(2-oxazoline) block copolymers, composed of hydrophilic poly(2-methyl-2-oxazoline) and hydrophobic poly(2-n-propyl-2-oxazoline) or poly(2-butyl-2-oxazoline-co-2-(3-butenyl)-2-oxazoline), was studied. The release profiles were fitted by zero-order and Ritger-Peppas models. The ultrasound increased the amount of released dexamethasone by 6% to 105% depending on the type of copolymer, the amount of loaded dexamethasone, and the stimulation time point. This study investigates for the first time the interaction between different poly(2-oxazoline)-based micelle formulations and ultrasound waves, quantifying the efficacy of such stimulation in modulating dexamethasone release from these nanocarriers.

The relations between crystalline structure and micromechanical properties of α-, β- and γ-phase of isotactic polypropylene (iPP) were investigated. The iPP samples with various crystalline phase compositions were prepared by a controlled high-pressure crystallization that enabled us to obtain not only α-iPP and β-iPP modifications, but also a series of almost pure γ-iPP samples with gradually changing morphology, crystallinity and lamellar thickness. The micromechanical properties were assessed by instrumented microindentation hardness testing (MHI), from which we determined indentation hardness (HIT), indentation modulus (EIT), indentation creep (CIT) and elastic part of the indentation work (ηIT). It was demonstrated that γ-iPP does not necessarily exhibit better mechanical performance than α- and β-iPP, as suggested by some previous studies, because the final properties are strongly influenced not only by the phase composition (i.e. by the content of α-, β- and γ-phase), but also by the overall crystallinity.

Here we report a novel method for the preparation of polymer nanocomposites containing in situ exfoliated graphene nanoplatelets. First, graphite particles were modified by sodium and ethylenediamine (en), yielding first-stage graphite intercalation compounds (GICs) containing [Na(en)] + complex between carbon sheets. After subsequent ion-exchange reaction of the intercalated complex with quaternary ammonium salt bearing methacrylamide group, GICs possessing polymerizable double bond were obtained. It was found that the extent of [Na(en)] + complex intercalation as well as the ion-exchange reaction was significantly dependent on the type of the graphite used (natural vs. synthetic). GICs derived from natural graphite were further employed in the synthesis of polymer nanocomposites. Using NMR and TEM it was confirmed that the methacrylamide group in GICs participated successfully in the process of copolymerization with 2-hydroxyethyl methacrylate and 2-ethylhexyl acrylate, resulting in the in situ GICs exfoliation. The prepared nanocomposite membranes were further characterized using X-ray diffraction, DSC and TGA. Gas permeability measurements on the polymer composites were also carried out, confirming that the initial GIC was present in an exfoliated form.

The chemically active heavier POSS homolog, the n-butylstannoxane dodacamer cage, shows unusual stabilizing properties during an oxidizing treatment of organic-inorganic hybrid polymer materials, into which it is incorporated as nano-building block. In this work, we dispersed Sn_POSS in several matrixes, which mainly had all-carbon backbones (based on polystyrene, polyacrylates and polyethers). Sn_POSS concentration was varied, and it was incorporated either as non-functional cage (blending), or via covalent bonding as a large co-monomer. The stannoxane cages' reactivity in the different matrixes was compared, and the authors propose matrix-dependent mechanisms of the stabilizing effect of Sn_POSS, which make possible to predict the behavior of this cage in different polymers, if their degradation mechanism and eventual reactivity of pendant groups can be estimated. Under oxidizing conditions, the studied matrixes yielded either pendant radicals on (at first) intact chains, or terminal radicals on ends of fragmented chains, depending on the exact polymer structure. The stannoxane cages, if present, subsequently underwent either crosslinking, or chain-repair reactions (fragmented chains re-connection) with the radical sites of the matrix. Another reaction type, which yielded additional crosslinking in the hybrids, was observed in case that the polymer matrix contained suitable pendant functional groups, which were able to react with Sn_POSS after activation either by heat or by oxidation.