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RATIONALE: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) is frequently used to analyze homo- and copolymers, i.e. for computing copolymer fingerprints. However, the oligomer abundances are influenced by mass discrimination, i.e. mass- and composition-dependent ionization. We have developed a computational method to correct the abundance bias caused by the mass discrimination. METHODS: MALDI-TOFMS in combination with computational methods was used to investigate three random copolymers with different ratios of styrene and isoprene. Furthermore, equimolar high- and low-mass styrene and isoprene homopolymers (2500 and 4200 Da) were mixed and also analyzed by MALDI-TOFMS. The abundances of both copolymers and homopolymers were corrected for mass discrimination effects with our new method. RESULTS: The novel computational method was integrated into the existing COCONUT software. The method was demonstrated using the measured styrene and isoprene co- and homopolymers. First, the method was applied to homopolymer spectra. Subsequently, the copolymer fingerprint was computed from the copolymer MALDI mass spectra and the correcting function applied. The changes in the composition are plausible, indicating that correction of copolymer abundances was reasonable. CONCLUSIONS: Our computational method may help to avoid erroneous conclusions when analyzing copolymer MS spectra. The software is freely available and represents a step towards comprehensive computational support in polymer science. Copyright © 2016 John Wiley & Sons, Ltd.

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Positively charged nanoparticles (NPs) are very interesting for biomedical and pharmaceutical applications, such as nonviral gene delivery. Here, the synthesis of SiO2 nanoparticles with a covalently grafted poly(2-ethyl-2-oxazoline) (PEtOx) shell (SiO2@PEtOx) is presented. PEtOx with a degree of polymerization of 20 and 38 is synthesized via microwave supported cationic ring-opening polymerization and subsequently end-functionalized with a triethoxysilyl linker for subsequent grafting to silica particles with hydrodynamic radii of 7, 31, and 152 nm. The resulting SiO2@PEtOx particles are characterized by using dynamic light scattering (DLS), transmission electron microscopy (TEM, cryoTEM), and scanning electron microscopy (SEM) to determine changes in particle size. Thermal gravimetrical analysis is used to quantify the amount of polymer on the silica surface. Subsequent in situ transformation of SiO2@PEtOx particles into SiO2@P(EtOx-stat-EI) (poly(2-ethyl-2-oxazoline-stat-ethylene imine) grafted silica particles) under acidic conditions inverts the surface charge from negative to positive according to ζ-potential measurements. The P(EtOx-stat-EI) shell could be used for the deposition of Au NP afterward.

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Polymer-based nanoparticles are promising drug delivery systems allowing the development of new drug and treatment strategies with reduced side effects. However, it remains a challenge to screen for new and effective nanoparticle-based systems in vitro. Important factors influencing the behavior of nanoparticles in vivo cannot be simulated in screening assays in vitro, which still represent the main tools in academic research and pharmaceutical industry. These systems have serious drawbacks in the development of nanoparticle-based drug delivery systems, since they do not consider the highly complex processes influencing nanoparticle clearance, distribution, and uptake in vivo. In particular, the transfer of in vitro nanoparticle performance to in vivo models often fails, demonstrating the urgent need for novel in vitro tools that can imitate aspects of the in vivo situation more accurate. Dynamic cell culture, where cells are cultured and incubated in the presence of shear stress has the potential to bridge this gap by mimicking key-features of organs and vessels. Our approach implements and compares a chip-based dynamic cell culture model to the common static cell culture and mouse model to assess its capability to predict the in vivo success more accurately, by using a well-defined poly((methyl methacrylate)-co-(methacrylic acid)) and poly((methyl methacrylate)-co-(2-dimethylamino ethylmethacrylate)) based nanoparticle library. After characterization in static and dynamic in vitro cell culture we were able to show that physiological conditions such as cell-cell communication of co-cultured endothelial cells and macrophages as well as mechanotransductive signaling through shear stress significantly alter cellular nanoparticle uptake. In addition, it could be demonstrated by using dynamic cell cultures that the in vivo situation is simulated more accurately and thereby can be applied as a novel system to investigate the performance of nanoparticle systems in vivo more reliable.

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The step-wise solution self-assembly of double crystalline organometallic poly(ferrocenyldimethylsilane)-block-poly(2-iso-propyl-2-oxazoline) (PFDMS-b-PiPrOx) diblock copolymers is demonstrated. Two block copolymers are obtained by copper-catalyzed azide-alkyne cycloaddition (CuAAC), featuring PFDMS/PiPrOx weight fractions of 46/54 (PFDMS30-b-PiPrOx75) and 30/70 (PFDMS30-b-PiPrOx155). Nonsolvent induced crystallization of PFDMS in acetone leads in both cases to cylindrical micelles with a PFDMS core. Afterward, the structures are transferred into water for sequential temperature-induced crystallization of the PiPrOx corona, leading to hierarchical double crystalline superstructures, which are investigated using scanning electron microscopy, wide angle X-ray scattering, and differential scanning calorimetry.

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The accurate characterization of synthetic polymer sequences represents a major challenge in polymer science. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is frequently used for the characterization of copolymer samples. We present the COCONUT software for estimating the composition distribution of the copolymer. Our method is based on Linear Programming and is capable of automatically resolving overlapping isotopes and isobaric ions. We demonstrate that COCONUT is well suited for analyzing complex copolymer MS spectra. COCONUT is freely available and provides a graphical user interface.

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Efficient delivery of short interfering RNAs reflects a prerequisite for the development of RNA interference therapeutics. Here, we describe highly specific nanoparticles, based on near infrared fluorescent polymethine dye-derived targeting moieties coupled to biodegradable polymers. The fluorescent dye, even when coupled to a nanoparticle, mimics a ligand for hepatic parenchymal uptake transporters resulting in hepatobiliary clearance of approximately 95% of the dye within 45 min. Body distribution, hepatocyte uptake and excretion into bile of the dye itself, or dye-coupled nanoparticles can be tracked by intravital microscopy or even non-invasively by multispectral optoacoustic tomography. Efficacy of delivery is demonstrated in vivo using 3-hydroxy-3-methyl-glutaryl-CoA reductase siRNA as an active payload resulting in a reduction of plasma cholesterol levels if siRNA was formulated into dye-functionalised nanoparticles. This suggests that organ-selective uptake of a near infrared dye can be efficiently transferred to theranostic nanoparticles allowing novel possibilities for personalised silencing of disease-associated genes.

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In the field of nanomedicine, cationic polymers are the subject of intensive research and represent promising carriers for genetic material. The detailed characterization of these carriers is essential since the efficiency of gene delivery strongly depends on the properties of the used polymer. Common characterization methods such as size exclusion chromatography (SEC) or mass spectrometry (MS) suffer from problems, e.g. missing standards, or even failed for cationic polymers. As an alternative, asymmetrical flow field-flow fractionation (AF4) was investigated. Additionally, analytical ultracentrifugation (AUC) and (1)H NMR spectroscopy, as well-established techniques, were applied to evaluate the results obtained by AF4. In this study, different polymers of molar masses between 10 and 120kgmol(-1) with varying amine functionalities in the side chain or in the polymer backbone were investigated. To this end, some of the most successful gene delivery agents, namely linear poly(ethylene imine) (LPEI) (only secondary amines in the backbone), branched poly(ethylene imine) (B-PEI) (secondary and tertiary amino groups in the backbone, primary amine end groups), and poly(l-lysine) (amide backbone and primary amine side chains), were characterized. Moreover, poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), poly(2-(amino)ethyl methacrylate) (PAEMA), and poly(2-(tert-butylamino)ethyl methacrylate) (PtBAEMA) as polymers with primary, secondary, and tertiary amines in the side chain, have been investigated. Reliable results were obtained for all investigated polymers by AF4. In addition, important factors for all methods were evaluated, e.g. the influence of different elution buffers and AF4 membranes. Besides this, the correct determination of the partial specific volume and the suppression of the polyelectrolyte effect are the most critical issues for AUC investigations.

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Methacrylate monomers were functionalized with a 4-hydroxythiazole chromophore and copolymerized with methyl methacrylate via RAFT. Nanoparticles of 120 and 500 nm in size were prepared without using stabilizers/surfactants. For comparative studies, preparative ultracentrifugation was applied for the separation into small and large particle fractions. All suspensions were characterized by DLS, AUC, and SEM and tested regarding their stability during centrifugation and re-suspension, autoclavation, and incubation in cell culture media. In vitro studies with mouse fibroblast cell line and differently sized NP showed a particle uptake into cells. Biocompatibility, non-toxicity, and hemocompatibility were demonstrated using a XTT assay, a live/dead staining, and an erythrocyte aggregation and hemolysis assay.

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This feature article provides, for the first time, an overview of the research that guided the way from fundamental studies of the thermo-responsive phase separation of aqueous polymer solutions to polymeric sensor systems. The incorporation of solvatochromic dyes into thermoresponsive polymers as well as the concepts of polymeric sensors are presented and discussed in detail.

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Thermoresponsive polymers that undergo a solubility transition by variation of the temperature are important materials for the development of 'smart' materials. In this contribution we exploit the solubility phase transition of poly(methoxy diethylene glycol methacrylate), which is accompanied by a transition from hydrophilic to hydrophobic, for the development of a fluorescent thermometer. To translate the polymer phase transition into a fluorescent response, the polymer was functionalized with pyrene resulting in a change of the emission based on the microenvironment. This approach led to a soluble polymeric fluorescent thermometer with a temperature range from 11 °C to 21 °C. The polymer phase transition that occurs during sensing is studied in detail by dynamic light scattering.

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The essential tasks of a department of interdisciplinary emergency medicine are the initial triage and assessment of vital function as well as the subsequent organization und initiation of emergency treatment. A previously defined set of diagnostic and therapeutic measures is carried out before the patient is allocated to an in-hospital clinical service and is admitted to a ward. Moreover, diagnosis and treatment for outpatients are performed. "Time" is a critical factor to be considered for all organizational and structural aspects of a department of interdisciplinary emergency medicine.

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