Mimicking Charged Host-Defense Peptides to Tune the Antifungal Activity and Biocompatibility of Amphiphilic Polymers.

Invasive fungal infections impose a substantial global health burden. They cause more than 1.5 million deaths annually and are insufficiently met by the currently approved antifungal drugs. Antifungal peptides are a promising alternative to existing antifungal drugs; however, they can be challenging to synthesize, and are often susceptible to proteases in vivo. Synthetic polymers which mimic the properties of natural antifungal peptides can circumvent these limitations. In this study, we developed a library of 29 amphiphilic polyacrylamides with different charged units, namely, amines, guanidinium, imidazole, and carboxylic acid groups, representative of the natural amino acids lysine, arginine, histidine, and glutamic acid. Ternary polymers incorporating primary ammonium (lysine-like) or imidazole (histidine-like) groups demonstrated superior activity against Candida albicans and biocompatibility with mammalian cells compared to the polymers containing the other charged groups. Furthermore, a combination of primary ammonium, imidazole, and guanidinium (arginine-like) within the same polymer outperformed the antifungal drug amphotericin B in terms of therapeutic index and exhibited fast C. albicans-killing activity. The most promising polymer compositions showed synergistic effects in combination with caspofungin and fluconazole against C. albicans and additionally demonstrated activity against other clinically relevant fungi. Collectively, these results indicate the strong potential of these easily producible polymers to be used as antifungals.

3D Printed Solid Polymer Electrolytes with Bicontinuous Nanoscopic Domains for Ionic Liquid Conduction and Energy Storage.

Solid polymer electrolytes (SPEs) offer several advantages compared to their liquid counterparts, and much research has focused on developing SPEs with enhanced mechanical properties while maintaining high ionic conductivities. The recently developed polymerization-induced microphase separation (PIMS) technique offers a straightforward pathway to fabricate bicontinuous nanostructured materials in which the mechanical properties and conductivity can be independently tuned. In this work SPEs with tunable mechanical properties and conductivities are prepared via digital light processing 3D printing, exploiting the PIMS process to achieve nanostructured ion-conducting materials for energy storage applications. A rigid crosslinked poly(isobornyl acrylate-stat-trimethylpropane triacrylate) scaffold provided materials with room temperature shear modulus above 400 MPa, while soft poly(oligoethylene glycol methyl ether acrylate) domains containing the ionic liquid 1-butyl-3-methylimidazolium bis-(trifluoromethyl sulfonyl)imide endowed the material with ionic conductivity up to 1.2 mS cm-1 at 30 °C. These features make the 3D-printed SPE very competitive for applications in all solid energy storage devices, including supercapacitors.

Traceless pH-Sensitive Antibody Conjugation Inspired by Citraconic Anhydride.

We introduce a pH-sensitive amide bond, inspired by citraconic anhydride, for the reversible conjugation of polymers to the lysine residues of proteins and antibodies. The pH sensitivity arises from a conformation lock at the end of the polymer, which we introduce by means of a Diels-Alder reaction, that positions a carboxylic acid close to the amide after conjugation occurs. The amide is stable over weeks at pH 7.4 but sensitive to hydrolysis at pH 5.5 and below, returning the amine to its original state. The pH sensitivity can be tuned by positioning secondary amide groups nearby. We use this approach to PEGylate an antibody to human serum albumin at high dilution and demonstrate successful recovery of the activity after hydrolysis at pH 5.5. These results offer a convenient and traceless approach to protein and antibody functionalization.

Effect of Star Topology Versus Linear Polymers on Antifungal Activity and Mammalian Cell Toxicity.

The global increase in invasive fungal infections and the emergence of drug-resistant strains demand the urgent development of novel antifungal drugs. In this context, synthetic polymers with diverse compositions, mimicking natural antimicrobial peptides, have shown promising potential for combating fungal infections. This study investigates how altering polymer end-groups and topology from linear to branched star-like structures affects their efficacy against Candida spp., including clinical isolates. Additionally, the polymers' biocompatibility is accessed with murine embryonic fibroblasts and red blood cells in vitro. Notably, a low-molecular weight star polymer outperforms both its linear polymeric counterparts and amphotericin B (AmpB) in terms of an improved therapeutic index and reduced haemolytic activity, despite a higher minimum inhibitory concentration against Candida albicans (C. albicans) SC5314 (16-32 µg mL-1 vs 1 µg mL-1 for AmpB). These findings demonstrate the potential of synthetic polymers with diverse topologies as promising candidates for antifungal applications.