Proton-Conducting Membranes from Polyphenylenes Containing Armstrong's Acid.

This study demonstrates the use of 1,5-naphthalenedisulfonic acid as a suitable building block for the efficient and economic preparation of alternating sulfonated polyphenylenes with high ion-exchange capacity (IEC) via Suzuki polycondensation. Key to large molar masses is the use of an all-meta-terphenyl comonomer instead of m-phenyl, the latter giving low molar masses and brittle materials. A protection/deprotection strategy for base-stable neopentyl sulfonates is successfully implemented to improve the solubility and molar mass of the polymers. Solution-based deprotection of polyphenylene neopentyl sulfonates at 150 °C in dimethylacetamide eliminates isopentylene quantitatively, resulting in membranes with high IEC (2.93 mequiv/g) and high proton conductivity (σ = 138 mS/cm). Water solubility of these copolymers with high IEC requires thermal cross-linking to prevent their dissolution under operating conditions. By balancing the temperature and time of the cross-linking process, water uptake can be restricted to 50 wt %, retaining an IEC of 2.33 mequiv/g and a conductivity of 85 mS/cm. Chemical stability is addressed by treatment of the membranes under Fenton's conditions and by considering barrier heights for desulfonation using density functional theory (DFT) calculations. The DFT results suggest that 1,5-disulfonated naphthalenes are at least as stable as sulfonated polyphenylenes against desulfonation.

Bivalent Peptide- and Chelator-Containing Bioconjugates as Toolbox Components for Personalized Nanomedicine.

While personalized therapy bears an enormous potential in cancer therapy, the development of flexible, tailorable delivery systems remains challenging. Here, we present a "tool-kit" of various avidin-based bioconjugates (BCs) for the preparation of personalized delivery systems. Corresponding BCs were synthesized using the self-assembly of avidin with various biotinylated ligands, such as one cationic glycodendrimer for dendriplex adsorption and two functional ligands for imaging (glycodendrimers with DOTA or NOTA units) or targeting (biotinylated PEG decorated with ligands). Substituting antibodies for targeting small molecules were coupled to biotin-PEG compounds for addressing the folate receptor (FR), epidermal growth factor receptor (EGFR), and prostate-specific membrane antigen (PSMA). After successful characterization and proof of good storage and redispersion properties of BCs, cytotoxicity assays and first in vivo imaging studies with 99mTc-complexing bioconjugates provide evidence that these BCs and their avidin analogues can be used as tool-kit components in theranostic systems for personalized medicine.

Mono- and Polyassociation Processes of Pentavalent Biotinylated PEI Glycopolymers for the Fabrication of Biohybrid Structures with Targeting Properties.

This study describes new mechanistic insights in the sequential polyassociation of streptavidin with biotinylated poly(ethyleneimine) glycopolymers and biotinylated PEGylated folic acid components for the preparation of biohybrid structures (BHS) for controlled targeting experiments. Characterization of the BHS revealed that during the formation and postfunctionalization of BHS, reversible dissociation and reassociation processes occur. The BHS are stable over weeks after finalizing the equilibrium-driven polyassociation process. Cellular uptake studies showed that this sequential polyassociation involving biotinylated PEGylated folic acid components does not lead to enhanced cellular uptake of the resulting BHS. In contrast, polyplexes, containing small interfering RNA and bioconjugates (1:1 molar ratio between biotinylated glycopolymer and monomeric streptavidin-lectin fusion protein), enabled us to control the targeting of tumor cells as revealed by knockdown of the tumor-associated protein survivin. Overall, this study demonstrates the high potential of (networklike) streptavidin-biotin interactions with a dynamic character in the formation of complex BHS and extracellular matrix materials.

Effect of the Structure of Therapeutic Adenosine Analogues on Stability and Surface Electrostatic Potential of their Complexes with Poly(propyleneimine) Dendrimers.

Poly(propyleneimine) glycodendrimers are proposed as nanocarriers for triphosphate forms of anticancer adenosine analogues to improve the efficiency of chemotherapy and to overcome drug resistance mechanisms. This approach has proven successful for fludarabine administration-an autonomous way of cellular entry of a nucleotide-dendrimer noncovalent complex enables an increase in the intracellular accumulation and cytotoxic activity of the active metabolite of the drug. However, the attempt to apply an analogous strategy for clofarabine results in the inhibition of drug activity. To better understand this phenomenon, characterization and comparison of drug-dendrimer complexes were needed to indicate the differences in their surface properties and the strengths of fludarabine-dendrimer and clofarabine-dendrimer interactions. Here, zeta potential measurements, ultrafiltration, and asymmetric flow field-flow fractionation are applied to determine the surface electrostatic potential and stability of nucleotide-dendrimer formulations. This approach significantly extends the authors' research on the complexation potential of perfectly branched macromolecules, ultimately explaining previously observed differences and their consequences.

Overcoming concealment effects of targeting moieties in the PEG corona: controlled permeable polymersomes decorated with folate-antennae for selective targeting of tumor cells.

In the context of diligent efforts to improve the tumor targeting efficiency of drug carriers, a shape-persistent polymersome which possess a pH-tunable membrane as well as folate targeting antennae is reported. The membrane of such polymersomes behaves as gate which undergoes "on" and "off" switches in response to pH stimuli. Thus, polymersomes can effectively prohibit the premature release of chemotherapeutic agents such as doxorubicin in physiological conditions, but promote drug release once they are triggered in the acidified endosomal compartment. Importantly, the folate moieties are installed on the surface of polymersomes as protruding antennae by doping the polymersomes with folate-terminated block copolymers designed to have longer PEG segments. Thereby, the folate moieties are freed from concealment and steric effects exerted by the dense PEG corona. The cellular uptake of the FA-antennae polymersomes by tumor cells is significantly enhanced facilitated by the freely accessible folate antennae; however, the normal cells record a low level of cellular uptake due to the stealth property of the PEG corona. Overall, the excellent biocompatibility, controlled permeability, targeted internalization, as well as selective cytotoxicity of such polymersomes set up the basis for properly smart carrier for targeted drug delivery.

Poly(ethylene oxide)-b-poly(3-sulfopropyl methacrylate) block copolymers for calcium phosphate mineralization and biofilm inhibition.

Poly(ethylene oxide) (PEO) has long been used as an additive in toothpaste, partly because it reduces biofilm formation on teeth. It does not, however, reduce the formation of dental calculus or support the remineralization of dental enamel or dentine. The present article describes the synthesis of new block copolymers on the basis of PEO and poly(3-sulfopropyl methacrylate) blocks using atom transfer radical polymerization. The polymers have very large molecular weights (over 10(6) g/mol) and are highly water-soluble. They delay the precipitation of calcium phosphate from aqueous solution but, upon precipitation, lead to relatively monodisperse hydroxyapatite (HAP) spheres. Moreover, the polymers inhibit the bacterial colonization of human enamel by Streptococcus gordonii, a pioneer bacterium in oral biofilm formation, in vitro. The formation of well-defined HAP spheres suggests that a polymer-induced liquid precursor phase could be involved in the precipitation process. Moreover, the inhibition of bacterial adhesion suggests that the polymers could be utilized in caries prevention.

Determination of low amounts of long-chain branches in polypropylene using a combination of chromatographic and rheological methods.

The focus of our investigations lies on the detection of low amounts of long-chain branching (LCB) in isotactic polypropylene (iPP) created by electron beam irradiation. The modified samples were investigated by rheological experiments in shear and elongational flow and by size-exclusion chromatography. The comparison of the results demonstrates the efficiency and the detection limits of these methods, particularly at very low degrees of long-chain branching. The combination of chromatographic and rheological methods enables a sensitive and comprehensive way for the characterisation of the long-chain branching phenomena.

Structure characterization of hyperbranched poly(ether amide)s. I. Preparative fractionation.

The focus of our investigation lies on the separation of typically broadly distributed hyperbranched poly(ether amide)s into narrow fractions of various molar masses. Their exact molar mass found via size-exclusion chromatography (SEC) with light uttering detection allows us to use these fractions for sample specific calibration in the SEC investigation of other hyperbranched samples. The analysis of the degree of branching, molar mass and viscosity behavior of the fractions gives a first indication about their molecular shape and the contribution of that shape to the overall viscosity. We determined the Mark-Houwink exponent for a hyperbranched sample using a number of narrow fractions which showed that an increase of molar mass leads to an increased molecular density.