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Magnetic particle imaging is an emerging tomographic method used for evaluation of the spatial distribution of iron‐oxide nanoparticles. In this work, the effect of the polymer coating on the response of particles was studied. Particles with covalently crosslinked coating showed improved signal and image resolution.

Mucin, a high molecular mass hydrophilic glycoprotein, is the main component of mucus that coats every wet epithelium in animals. It is thus intrinsically biocompatible, and with its protein backbone and the o-glycosidic bound oligosaccharides, it contains a plethora of functional groups which can be used for further chemical modifications. Here, chain-growth and step-growth (thiol-ene) free-radical cross-linked hydrogels prepared from commercially available pig gastric mucin (PGM) are introduced and compared as cost-efficient and easily accessible alternative to the more broadly applied bovine submaxillary gland mucin. For this, PGM is functionalized with photoreactive acrylate groups or allyl ether moieties, respectively. Whereas homopolymerization of acrylate-functionalized polymers is performed, for thiol-ene cross-linking, the allyl-ether-functionalized PGM is cross-linked with thiol-functionalized hyaluronic acid. Morphology, mechanical properties, and cell compatibility of both kinds of PGM hydrogels are characterized and compared. Furthermore, the biocompatibility of these hydrogels can be evaluated in cell culture experiments.

Enhancing the colloidal stability of silver nanoparticles (AgNPs) is crucial to maintain their unique properties allowing broad application of these NPs. Stabilization of AgNPs is usually achieved by surface modification with thiol containing polymers showing limitations owing to the nucleophilic and oxidative character, whereas chemical inert thioethers have so far received little attention. Herein, AgNPs coated with mono‐ and multivalent thiol‐ and thioether polymers are prepared to systematically investigate the adsorption kinetics onto the silver surface as well as the colloidal stability after exposure to different conditions relevant for biomedical application, such as freeze‐drying and treatment under physiological conditions. Although the thioether polymers show a slower immobilization onto AgNPs, the same or mostly even better stabilization is exhibited than for the thiol analogs. In addition, the polymer surface coverage and the polymeric arrangement of these polymers on AgNPs are calculated, as they supposedly influence the stability.

Aspergillus fumigatus is the opportunistic fungus responsible for a variety of serious and often lethal diseases of immunocompromised patients, such as invasive aspergillosis, aspergilloma, and allergic bronchopulmonary aspergillosis. Therapeutic options for such fungal infections are limited due to the high toxicity of currently available drugs. Herein, the potency of nanogels (NGs) is assessed for uptake and delivery of antifungal therapeutics. Therefore, poly(glycidol)‐based NGs are prepared by surfactant‐free inverse nanoprecipitation. Uptake studies conducted with fluorescently labeled particles demonstrate internalization by fungi in their hyphal form. In addition, loading with both amphiphilic and hydrophobic fluorescent dyes as model drugs show efficient delivery of the fluorescent dyes into the fungus. Finally, particles are loaded with the antifungal drug itraconazole by soaking lyophilized NGs in the drug solution (breathing‐in method). Efficient delivery of the drug by nanoprecipitated NGs, improved fungicidal activity, and reduced side effects as compared with the drug itself are shown.

Multiple myeloma is a common plasma-cell-derived hematologic neoplasm. While the delivery of growth-inhibiting miRNA to multiple myeloma cells would be a promising strategy to evaluate treatment options, most multiple myeloma cells are transfection-resistant with established methods. Nonviral nanoparticulate transfection systems are particularly promising in this context, but so far struggle with transfection and knockdown efficiency. Here, we present poly(glycidol)-based nanogels with covalently bound cell-penetrating peptide TAT (transactivator of transcription from HIV). TAT facilitated a varying internalization efficiency of the nanogels depending on the cell line. The positively charged peptide also served as complexation agent for miRNA and enabled covalent binding of the TAT/miR-34a complex in the nanogels. These TAT/miRNA-loaded nanogels delivered and released miR-34a with high efficiency into OPM-2 multiple myeloma cells that are known as transfection-resistant. Delivery resulted in efficient downregulation of known target genes such as Notch1, Hey1, Hes6, and Hes1. Thus, these nanogel constructs offer a new tool to enhance gene delivery into multiple myeloma cells with immediate value in cancer research.

The incidence of life-threatening invasive fungal infections (IFIs) has increased significantly in recent years. Current therapeutic options for IFIs are limited. Only four major classes of antifungal agents are available to clinicians, namely polyenes, azoles, echinocandins, and flucytosine. These antifungals have particular drawbacks, including toxicity, drug-drug interactions, and increasing antifungal resistance. Consequently, there is an urgent need for new antifungals to combat IFIs. This review illuminates new classes of synthetic antifungal drugs under preclinical and clinical investigations that have novel mechanisms of action; it also examines innovative strategies for the in vivo delivery of antifungal drugs. It is imperative to expand the pipeline of antifungals to tackle emerging fungal resistance against conventional antimycotic drugs, toxicity, and drug-drug interactions. This unmet medical need should not be underappreciated.

Invasive aspergillosis is a serious threat to immunodeficient and critically ill patients caused mainly by the fungus

We report on the structure of a system of wedge-shaped molecules with a sulfonic end group incorporated into the both the homopolymer P2VP and the block copolymer P2VP-b-PEO, at degrees of complexing of 25%, 50%, and 100%. From X-ray scattering in the bulk all three homopolymer complexes reveal a lamellar phase, which is, however, for 100% mixed with a hexagonal phase. In agreement with earlier work on thin films, the corresponding block copolymers show all a structure of PEO cylinders perpendicular to lamellae of the ligands. Between 25% and 50% neutralization the packing changes from relatively loose layers consisting of several backbone chains with ligands for 25% to a situation of single backbones with highly stretched ligands for higher degrees of neutralization. In the latter cases crystallization of the confined PEO blocks is strongly reduced.

Extracellular RNAs (ex-RNAs) are secreted by cells through different means that may involve association with proteins, lipoproteins or extracellular vesicles (EV). In the context of parasitism, ex-RNAs represent new and exciting communication intermediaries with promising potential as novel biomarkers. In the last years, it was shown that helminth parasites secrete ex-RNAs, however, most work mainly focused on RNA secretion mediated by EV. Ex-RNA study is of special interest in those helminth infections that still lack biomarkers for early and/or follow-up diagnosis, such as echinococcosis, a neglected zoonotic disease caused by cestodes of the genus Echinococcus. In this work, we have characterised the ex-RNA profile secreted by in vitro grown metacestodes of Echinococcus multilocularis, the casuative agent of alveolar echinococcosis. We have used high throughput RNA-sequencing together with RT-qPCR to characterise the ex-RNA profile secreted towards the extra- and intra-parasite milieus in EV-enriched and EV-depleted fractions. We show that a polarized secretion of small RNAs takes place, with microRNAs mainly secreted to the extra-parasite milieu and rRNA- and tRNA-derived sequences mostly secreted to the intra-parasite milieu. In addition, we show by nanoparticle tracking analyses that viable metacestodes secrete EV mainly into the metacestode inner vesicular fluid (MVF); however, the number of nanoparticles in culture medium and MVF increases > 10-fold when metacestodes show signs of tegument impairment. Interestingly, we confirm the presence of host miRNAs in the intra-parasite milieu, implying their internalization and transport through the tegument towards the MVF. Finally, our assessment of the detection of Echinococcus miRNAs in patient samples by RT-qPCR yielded negative results suggesting the tested miRNAs may not be good biomarkers for this disease. A comprehensive study of the secretion mechanisms throughout the life cycle of these parasites will help to understand parasite interaction with the host and also, improve current diagnostic tools., Author summary Extracellular RNAs (ex-RNAs) are secreted by cells through association with proteins or extracellular vesicles (EV). In the context of parasitism, ex-RNAs represent novel communication intermediaries with promising potential as biomarkers. In order to better understand the role ex-RNAs may play in the context of the zoonotic disease echinococcosis, we have characterised the RNA profile secreted by the larval stage (metacestode) of Echinococcus multilocularis. By analysing the products secreted towards the extra- and intra-parasite milieus, we demonstrate that the metacestode displays a polarized secretion of different classes of small non-coding RNAs (sRNAs). In addition, we show that EV secretion occurs mainly towards the inner fluid of the metacestodes. Interestingly, we confirm the presence of host sRNAs in the intra-parasite milieu, implying their internalization and transport through the tegument. Finally, the detection of Echinococcus miRNAs in patient samples yielded negative results suggesting the tested miRNAs may not be good biomarkers for this disease. In summary, our results provide a detailed description of the ex-RNA landscape of the E. multilocularis metacestode together with information on the distribution of the detected RNA classes in different extracellular compartments. This information is of importance to better understand host-parasite interaction and also, to improve current diagnostic tools.

Polycyclische aromatische Kohlenwasserstoffe (PAHs) sind allgegenwartige Schadstoffe in der Umwelt und insbesondere im Trinkwasser. Nach Kontakt von PAHs mit DNA bilden sich als erster Schritt der toxischen Wirkung schnell stabile PAH-DNA-Zusammenlagerungen. In dieser Arbeit wurden hydrophile DNA-Nanogele hergestellt, um den Komplexierungsprozess als eine biomimetische Reinigungsmethode zu nutzen. Der Ansatz ist dabei nicht auf die Adsorption an der Nanogeloberflache beschrankt, sondern beruht auf der Wechselwirkung zwischen PAHs mit der gesamten Netzwerkstruktur der mit Wasser gequollenen Hydrogelnetzwerke. Die Aufnahme von bis zu 720 μg PAH pro Gramm DNA belegt eine Reinigungskapazitat von 1 mg DNA pro Liter Wasser mit einer kritischen, potentiell krebsauslosenden PAH-Konzentration von 600 ng L−1. Aufgrund der kurzen Diffusionswege erfolgt die schnelle Aufnahme von PAHs mit einer 50 %igen Beladung nach 15 min. Daneben konnten DNA-Nanogele fur die allgemeine Entgiftung von Trinkwasser hilfreich sein, da die meisten bekannten Molekule, die starke Wechselwirkungen mit DNA zeigen, Mutagene sind.

International audience; We studied the effect of subtle changes in side-chain chemistry and labelling with near infrared fluorophores of nanogels (NGs) prepared from thiolated poly(glycidol) on in vivo biodistribution in mice bearing human breast tumor xenografts. The stability and amphiphilic character of the side chain as well as labelling clearly influenced tumor targeting and overall biodistribution.

This study presents the reactive self-assembly of isocyanate functional and amphiphilic six-arm, star-shaped polyether prepolymers in water into nanogels. Intrinsic molecular amphiphilicity, mainly driven by the isophorone moiety at the distal endings of the star-shaped molecules, allows for the preparation of spherical particles with an adjustable size of 100-200 nm by self-assembly and subsequent covalent cross-linking without the need for organic solvents or surfactants. Covalent attachment of a fluorescence dye and either the cell-penetrating TAT peptide or a random control peptide sequence shows that only TAT-labeled nanogels are internalized by HeLa cells. The nanogels thus specifically enter the cells and accumulate in the perinuclear area in a time- and concentration-dependent manner.

Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. (C) 2016 Elsevier Inc. All rights reserved.

Nanogels consist of three dimensionally cross-linked hydrophilic polymer chains and can thus be easily modified through functionalization of the polymeric building blocks, for example to yield stimuli-sensitive materials. For drug transport and intracellular release, redox-sensitive systems are especially of interest, as the intracellular space is reductive. In this study, parameters that allow preparation of nanogels with tunable size between 150 and 350 nm are systematically evaluated and identified. Most importantly, a new and mild oxidation catalyst, alloxan, is introduced for the preparation of the nanogels. This broadens the range of possible payloads to more-sensitive molecules. Particle stability, degradation in cytosolic conditions, and cytocompatibility in concentrations up to 10 mg · mL(-1) are demonstrated.

Redox-sensitive materials have received dramatically increasing interest over the past years.1 Disulfide cross-linked colloidal networks are particularly appealing, as they are rapidly reduced to thiols under the reductive environment inside cells, allowing the quantitative release of the payload incorporated within the particles.2 Moreover, disulfide cross-linked hydrogels as three-dimensional cell-culture scaffolds can be degraded under cytocompatible mild reductive conditions without affecting the vitality of the embedded cells.3

Redoxsensitive Materialien sind verst rkt in den wissenschaftlichen Fokus ger ckt. Insbesondere mit Disulfiden verkn pfte kolloidale Netzwerke werden intensiv erforscht, da sie unter den reduktiven Bedingungen im Zellinneren schnell zu ihren Thiol-funktionalisierten Bausteinen reduziert werden. Dies ermcglicht eine nahezu quantitative Freisetzung von in den Partikeln eingebautenMolek len in Zellen. Dar ber hinaus dienen Disulfid-verkn pfte Hydrogele als Zelltr germaterialien, die unter milden reduktiven, zytokompatiblen Bedingungen gezielt abgebaut werden kcnnen, ohne die Vitalit t der darin eingeschlossenen Zellen zu beeintr chtigen. Disulfid-verkn pfte Polymernetzwerke lassen sich durch direkte Polymerisation Disulfid-funktionalisierter Monomere, mittels Disulfid-haltiger Vernetzer oder durch oxidative Verkn pfung Thiol-funktionalisierter Bausteine (Thiomere) herstellen. Dabei erlaubt nur der letztgenannte Ansatz einen unmittelbaren kovalenten Einbau Thiol-funktionalisierter Molek le (wie Cystein-haltige Peptidsequenzen) w hrend der Bildung des Netzwerkes. Eine Gelbildung von Thiomeren durch blosen Kontakt mit Luftsauerstoff ist mcglich, aber zu langsam f r die definierte Herstellung von Nanopartikeln mit den meisten blichen Methoden sowie f r eine homogene Zellverteilung in Hydrogelen. Daher finden Oxidationskatalysatoren wie das weit verbreitete Wasserstoffperoxid (H2O2) zur Verk rzung der Reaktionszeiten Anwendung. Das starke Oxidationspotential des H2O2 bewirkt jedoch eine Oxidation von Thiolen ber Disulfide hinaus, was die Auswahl der Molek le, die w hrend der Netzwerkbildung anwesend sein kcnnen, begrenzt und die vollst ndige Abbaubarkeit der Netzwerke durch reduktive Stimuli beeintr chtigt. Im Gegensatz dazu kcnnen Enzyme unter milden Bedingungen mit einzigartiger Selektivit t und ohne zus tzliche chemische Vernetzer eingesetzt werden. Eine grose Anzahl von Studien besch ftigt sich daher mit enzymvermittelter Hydrogelbildung. So haben L tolf und Mitarbeiter in Analogie zum nat rlichen Vernetzungsprozess des Fibrins Transglutaminasen zur Vernetzung von Hydrogelen verwendet, die mit Zelladh sionspeptiden versehen werden kcnnen und anschliesend durch Matrix-Metalloproteasen abbaubar sind. Ein k rzlich erschienener bersichtsartikel zur enzymatischen Vernetzung von Hydrogelen zeigt, dass diese Methode bisher generell zu Gelen gef hrt hat, die entweder durch enzymatisch katalysierten Bruch kovalenter Bindungen, oder durch harsche und nicht zytokompatible chemische Bedingungen wie drastische pHnderungen abbaubar sind. Die in der Biotechnologie weit verbreitete Meerrettichperoxidase (HRP) ist eines der am besten untersuchten oxidationskatalysierenden Enzyme. Der konventionelle HRP-Zyklus wird durch die Reaktion von HRP mit H2O2 initiiert, woraus hochreaktive Intermediate als starke Oxidationsmittel resultieren. In Gegenwart von Thiolen werden dadurch Thiyl-Radikale gebildet, die zu Disulfiden dimerisieren oder mit Thiolaten zum Disulfid-Radikal reagieren kcnnen, das schlieslich durch Reaktion mit Sauerstoff zu einer Disulfidgruppe umgesetzt wird. Daher wird f r eine HRP-unterst tzte Vernetzung normalerweise die Zugabe von H2O2 benctigt, um die Reaktion zu initiieren. [15–17] Unter aeroben Bedingungen ist dies jedoch nicht notwendig, da H2O2 w hrend der Autoxidation von Thiolen in stcchiometrischen Mengen gebildet wird. Dieses kann dann die Bildung von Disulfiden katalysieren, wobei das absolute stcchiometrische Verh ltnis eine weitere Oxidation der Disulfide verhindert. Hier beschreiben wir die HRP-vermittelte Herstellung von funktionalen, redoxsensitiven, Disulfid-vernetzten Hydrogelen und Nanogelen durch oxidative Kupplung von Thiomeren ohne Zugabe von H2O2. Thiol-funktionalisierte lineare Poly(glycidole) (Mn= 6100 gmol ; HS-PG) wurden hierzu als hydrophile und zytokompatible Gel-Vorstufen gew hlt. Homogene Lcsungen von HS-PG in phosphatgepufferter Salzlcsung (PBS; 30 Gew.-%, pH 7.4, 8.0, 8.5) zeigten bei Raumtemperatur ohne Zugabe von HRP keine Gelbildung innerhalb von 24 Stunden. In Gegenwart von HRP gelierte das System jedoch bei pH 8.5 innerhalb von maximal 4 Stunden (Abbildung 1). Die Gelbildung wurde dabei in situ mithilfe eines Oszillationsrheometers verfolgt. Ein typisches Zeitprofil der Gelierung ist durch zwei Phasen charakterisiert. W hrend einer initialen Anlaufphase von [*] S. Singh, F. Topuz DWI e.V. und Institut f r Technische und Makromolekulare Chemie RWTH Aachen Forckenbeckstrase 50, 52056 Aachen (Deutschland)

Polycyclic aromatic hydrocarbons (PAHs) are combustion-related pollutants and are ubiquitous in the environment, including in sources of drinking water. Upon contact with DNA, stable PAH-DNA adducts form rapidly as the first step towards their toxic effects. In this work, we prepared hydrophilic DNA nanogels to exploit this generic complexation process as a biomimetic scavenging method. This approach relies on interaction between PAHs and the complete network that constitutes the water-swollen nanogels, and is not restricted to interfacial adsorption. Up to 720 μg of PAH per gram of DNA nanogel are taken up, meaning that 1 mg of DNA nanogel is sufficient to purify a liter of water containing the critical PAH concentration for cancer risk (600 ng L(-1) ). As a result of short diffusion pathways, PAH uptake is rapid, reaching 50 % loading after 15 minutes. Beyond PAHs, DNA nanogels may be useful for the generic detoxification of water containing genotoxins, since most known molecules that strongly associate with DNA are mutagenic.

The preparation of micelles based on polystyrene-block-polyglycidol (PS-b-PG) in a selective solvent and their loading with titanium(IV)-isopropoxide, a precursor for titanium dioxide, nanoparticles is described. The formation of micelles was studied with scanning force microscopy (SFM) and transmission electron microscopy (TEM), before and after loading with the titanium alcoholate. Interaction of the hydroxyl groups of the polyglycidol side chains with titanium(IV)-isopropoxide leads to covalent cross-linking of the micellar core. Formation of micelles with frozen cores was verified by dynamic light scattering. The cross-linked micelles were coated onto a substrate and treated with plasma to achieve hexagonally ordered titanium dioxide nanoparticles.

Melt electrospinning is one aspect of electrospinning with relatively little published literature, although the technique avoids solvent accumulation and/or toxicity which is favoured in certain applications. In the study reported, we melt-electrospun blends of poly(ε-caprolactone) (PCL) and an amphiphilic diblock copolymer consisting of poly(ethylene glycol) and PCL segments (PEG-block-PCL). A custom-made electrospinning apparatus was built and various combinations of instrument parameters such as voltage and polymer feeding rate were investigated. Pure PEG-block-PCL copolymer melt electrospinning did not result in consistent and uniform fibres due to the low molecular weight, while blends of PCL and PEG-block-PCL, for some parameter combinations and certain weight ratios of the two components, were able to produce continuous fibres significantly thinner (average diameter of ca 2 µm) compared to pure PCL. The PCL fibres obtained had average diameters ranging from 6 to 33 µm and meshes were uniform for the lowest voltage employed while mesh uniformity decreased when the voltage was increased. This approach shows that PCL and blends of PEG-block-PCL and PCL can be readily processed by melt electrospinning to obtain fibrous meshes with varied average diameters and morphologies that are of interest for tissue engineering purposes. Copyright © 2010 Society of Chemical Industry

Thiofunctional polymers are the established standard for the coating and biofunctionalization of gold nanoparticles (AuNPs). However, the nucleophilic and oxidative character of thiols provokes polymeric crosslinking and significantly limits the chemical possibilities to introduce biological functions. Thioethers represent a chemically more stable potential alternative to thiols that would offer easier functionalization, yet a few studies in the literature report inconclusive data regarding the efficacy of thioethers to stabilize AuNPs in comparison to thiols. A systematic comparison is presented of mono- versus multivalent thiol- and thioether-functional polymers, poly(ethylene glycol) versus side chain functional poly(glycidol) (PG) and it is shown that coating of AuNPs with multivalent thioether-functional PG leads to superior colloidal stability, even under physiological conditions and after freeze-drying and resuspension, as compared to thiol analogs at comparable polymer surface coverages. In addition, it is shown that a wide range of functional groups can be introduced in these polymers. Using diazirine functionalization as example, it is demonstrated that proteins can be covalently immobilized, and that conjugation of antibodies via this strategy enables efficient targeting and laser-irradiation induced killing of cells.

Porous coordination polymers, in particular flexible porous coordination polymer networks that change their network structure on guest adsorption, have enormous potential in applications involving selective storage, separation and sensing. Despite the expected significant differences in their adsorption properties, porous coordination polymer nanocrystals remain largely unexplored, and there have been no reports about studies on flexible porous coordination polymer nanocrystals, mainly due to a lack of preparation methods. Here, we present a new technique for the rapid preparation of porous coordination polymer nanocrystals that combines non-aqueous inverse microemulsion with ultrasonication. Uniform nanocrystals of {[Zn(ip)(bpy)]}(n) (ip = isophthalate, bpy = 4,4'-bipyridyl; CID-1), a flexible porous coordination polymer, have been prepared by this method and analysed using field-emission scanning electron microscopy, energy-dispersive X-ray analysis, infrared spectroscopy, Raman spectroscopy and X-ray powder diffraction. A model for particle formation and growth is presented and discussed. Adsorption experiments with methanol show that the overall adsorption capacities of nanoparticles and bulk are almost identical, but the shapes of the sorption isotherms differ significantly and the adsorption kinetics increase dramatically.

Stable hollow polymeric nanocapsules with a cross-linked shell were prepared through an interfacially confined copolymerization of a monovinyl monomer and divinyl cross-linker via an activator generated by electron transfer atom transfer radical polymerization (AGET ATRP) in a miniemulsion system. An amphiphilic block copolymer poly(ethylene oxide)-b-poly(n-butyl methacrylate) (PEO−PBMA−Cl) was used as a stabilizer/macroinitiator. The amphiphilic nature of the macroinitiator ensures that the polymerization starts from the aqueous/monomer droplet interface with polymer chains slowly growing inward in a controlled manner by an AGET initiated ATRP. Characterization of the resulting particles by TEM, Cryo-SEM, and AFM provided direct evidence that nanoparticles with a hollow structure were successfully prepared. Introduction of cross-linking units to the shell of the particles improved the stability of the particles, which could be easily redispersed in some common organic solvents.

Hydrogel nanoparticles, so called nanogels, are hydrophilic crosslinked polymeric particles with submicrometer size. They combine characteristics of hydrogels like biocompatibility, high-water content as well as tunable chemical and mechanical properties with the features of nanoparticles such as high-surface area and overall sizes in the range of cellular compartments. These properties make them intriguing candidates for entrapment of hydrophilic bioactive molecules such as DNA or proteins to provide a hydrophilic environment and protect them from degradation. So far, little attention has been paid to the size dependence on the cell uptake and pharmacokinetics. A prerequisite for this is, however, synthetic access to well-defined particles. Several techniques have been used for the preparation of microgels such as precipitation polymerization, photolithography, micromolding, microfluidics, and inverse emulsion techniques. Polymerization in inverse miniemulsion is one way that allows preparation of gel particles with controlled size in the submicron range. However, syntheses of nanogels in inverse emulsions are mostly done by radical polymerization techniques and only little work has been reported on crosslinking of well-defined prepolymers. Such a prepolymer condensation concept based on hydrophilic multithiolfunctionalized oligomers and polymers will be particularly suitable for incorporating peptides and proteins in particles that are stable in extracellular physiological conditions but degrade after uptake by cells within the reductive environment of the cytosol where for example glutathione, a tripeptide with a free thiol group, readily cleaves disulfides to thiols. In contrast to radical polymerization techniques, oxidative coupling of thio-functional macromers in inverse miniemulsion allows the attachment of cysteine-terminated peptide sequences as the free thiol groups do not interfere with the polymerization. As a best example so far, highmolecular weight, thiol-functionalized hyaluronic acid has been crosslinked in inverse miniemulsion by oxidation. However, variation of functionality or molecular architecture of the gel precursor could not be achieved. Here, we present synthesis and characterization of biocompatible and degradable nanogel carriers composed of thiol-functionalized polymers based on starshaped poly(ethylene oxide-stat-propylene oxide) (sP(EO-stat-PO)) and linear poly(glycidol) (PG). Nanogel particles are prepared by crosslinking the polymers in inverse miniemulsion via oxidation of thiol groups to disulfide bonds. Synthesis and characterization of the gel precursors, preparation of the nanogels, and their characterization regarding particle size distribution in solution and in the dried state, chemical composition, degradation behavior as well as in vitro biocompatibility studies are presented and discussed. Reduction-sensitive degradation of the nanogels in cytosolic conditions, cytocompatibility, hydrophilicity, as well as a crosslinking chemistry that allows for the introduction Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 47, 5543–5549 (2009)

Wedge-shaped molecules with a sulfonic group at the tip have been incorporated into a poly(2- vinylpyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) diblock copolymer via proton transfer at different degrees of neutralization. The protonation of P2VP was monitored by means of Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The thin film morphology of the complexed block copolymers has been studied by scanning force microscopy and X-ray reflectivity. The complexes exhibit strongly microphase-segregated patterns comprising smectic layers of the complexed P2VP blocks, oriented parallel to the substrate throughout the whole film with the embedded PEO domains. For the complex with a degree of neutralization of 0.50 ordered amorphous PEO cylinders are observed oriented perpendicular to the substrate. For a degree of neutralization equal to 0.25 initially also perpendicular PEO cylinders are formed, but upon solvent-vapor annealing they partially merge, resulting in a mixed lamellar-cylindrical morphology. In all cases an extra surface layer is formed at the substrate. Thus, for the first time we have demonstrated that a block copolymer thin film structure can easily be controlled by the degree of neutralization of one of the blocks.

Highly ordered hexagonal nanopatterns of gold clusters on glass substrates were used as anchoring points for the specific attachment of fluorescence dyes and proteins labeled with fluorescence dyes. Thiol- or disulfide-containing linker molecules were used for the binding to the gold dots. In order to ensure specific binding on the gold dots only, the surface area in between the dots was protected against unspecific adsorption. For the attachment of polar low-molecular-weight fluorescence dyes, an octadecyltrichlorosilane self-assembled monolayer was prepared on the surface in between the gold dots, whereas a layer prepared from star-shaped poly(ethylene oxide-stat-propylene oxide) prepolymers was used to prevent unspecific adsorption of proteins between the gold dots. Fluorescence microscopy proved the specific binding of the dyes as well as of the proteins. Scanning force microscopy studies show that each gold dot is only capable of binding one protein at a time.

Thermo- and pH-responsive microgels were prepared from solubilized native elastin by crosslinking of the elastin lysine residues with poly(ethylene glycol) diglycidyl ether (PEG-DGE) and with bis(sulfosuccinimidyl) suberate (BS3). In the first case, a peptide-PEG conetwork was obtained whereas, in the second case, the elastin peptides were interlinked with hydrophobic bridges. The structure of the microgels was controlled by the ratio of crosslinker to elastin and by performing the crosslinking reaction in an inverse minielemulsion, yielding particles with a diameter in the submicron range. Depending on the degree of crosslinking, the hybrid microgels exhibited a volume change transition at 37 and 35.5°C and pH responsivity in the range of 5–7 for microgels crosslinked with PEG-DE and BS3, respectively. This temperature- and pH-responsive behavior can be assigned to the well-investigated coacervation of elastin peptides, demonstrating that the elastin functionality is abolished only by rather dense crosslinking. In spite of the broad distribution in the molecular weight of the elastin molecules, the microgels remained soluble. Light scattering and sedimentation experiments demonstrated that the coacervation occurred predominantly intramolecularly, i.e., by collapse in the core while the corona stabilized the colloidal dispersion against precipitation. Preliminary experiments were conducted to evaluate the suitability of these microgels for use as a drug-release system and demonstrated cytocompatibility, enzymatic degradability by elastase, and entrapping and slow release of a water-soluble biopolymer (Texas Red-labeled dextran with M w = 70,000). In summary, we present an easy entry to functional biohybrid microgels, where the responsiveness to temperature and pH can be exploited further for application of the microgel as a drug carrier.

Nano- and Microgels are predominantly prepared using radical polymerization techniques. This chapter reviews alternative approaches to microgel preparation based on addition reactions of functional oligomers and polymers. This allows preparation of microgels under physiological conditions and in the presence of biologically active molecules without affecting their function. This method is therefore predominantly used to synthesize microgels for biomedical applications. Different crosslinking chemistries that have been used in this context are presented and discussed with regard to reaction conditions and stability of the reaction product. Microgels that have been prepared by these techniques are divided into two groups. Natural polymers used for the preparation of microgels are described first, followed by artificial prepolymers that are suitable for the preparation of microgels. The different preparation methods as well as the resulting microgels and their properties are presented and discussed.

Isocyanate-terminated six armed star shaped macromers with a statistical copolymer backbone consisting of 80% EO and 20% PO have previously demonstrated excellent protein and cell repellence as nano-layered surfaces. In this study, various macromers are mixed with water and provide a spectrum of materials that range from particles to uniform hydrogels. Due to hydrophobic end groups, 3 kDa molecular weight macromers result in micro and nano-particles, while 18 kDa macromers completely dissolve and consequently uniform, transparent, high water content hydrogels are formed. Oriented channels may be induced into these hydrogels through the controlled freezing of water in the preformed hydrogel.

Lateral phase segregation of block copolymers in ultra-thin films results in highly orderedarrays at interfaces. In this brief review we focus on PS-b-P2VPand PS-b-P4VP block copolymers. Selective solvents and polar solidsubstrates lead to a brush surface formed by adsorption of free polymer chains in solution followedby adsorption of whole micelles upon withdrawal of the sample from the solution. These laterallyhighly ordered patterns are obtained by rapid solvent evaporation and are thermodynamically not stable.In the second case presented two-dimensional surface micelles of poly(styrene)-block-poly(N-alkyl-4-vinylpyridinum iodide) are formed by spreading a solutionin a slightly selective solvent mixture onto the water/air interface. The resulting patternmorphology strongly depends on the surface pressure and the length of the alkyl chain used for quaternization.These patterns can be transferred to solid substrates without structural changes. In contrast, polymerdeposition onto mica from nonselective solvents is controlled by the polymer-surface interaction andthe resulting patterns are induced by the surface (Surface-Induced NanoPATterns, SINPATs). The PVPblock adsorbs strongly on mica in a two-dimensional coil whereas the PS block dewets the adsorbedPVP layer forming isolated clusters. These patterns are thermodynamically stable. As one possibleapplication, Ti/SINPAT composites have been successfully used as etch masks allowing the transferof regular structures of nanometer size into substrates.

Hydrogels are fascinating materials with high water content and low surface friction that can be tailored for numerous applications. However, their practical application is often hampered by an intrinsic mechanical weakness. Strategies for mechanically strong hydrogels have been developed, with double network (DN) hydrogels reaching remarkable compression resistance, although so far with loss of these properties under repeated compression. In this study we present DN hydrogels composed of cross-linked six arm star-shaped poly(ethylene oxide-stat-propylene oxide) (sPEOPO) primary networks and polyacrylamide (PAAm) as secondary network. These hydrogels possess high water content (>90 w/w%) and high compression strength of up to 5.6 MPa. Most importantly, they show a fully reversible behaviour in repeated loading–unloading experiments with 1 MPa maximal stress, which we attribute to the partial healing capacity of the primary network and the overall macroporous morphology of the gels.