Beyond , Pharmaceutical Molecule Production in Cell-Free Systems and the Use of Noncanonical Amino Acids Therein.

Throughout history, we have looked to nature to discover and copy pharmaceutical solutions to prevent and heal diseases. Due to the advances in metabolic engineering and the production of pharmaceutical proteins in different host cells, we have moved from mimicking nature to the delicate engineering of cells and proteins. We can now produce novel drug molecules, which are fusions of small chemical drugs and proteins.

pH-sensitive polyglycerol nanogels for periodontitis treatment through antibacterial and pro-angiogenesis action.

Periodontitis is a microbe-driven inflammatory disease leading to bone resorption and tissue destruction. We propose a dual-functional nanogel complex armed with the antimicrobial drug triclosan (TCS) and the pro-angiogenesis medication deferoxamine (DFO) for combating microbial pathogens and promoting tissue regeneration. The nanogel system (NG-TCS-DFO) that we fabricated from linear polyglycerol exhibits well-defined spherical morphology and a positively charged surface for bacteria adhesion.

Deciphering Polymer Interactions in Bioconjugates with Different Architectures by Structural Analysis via Time-Resolved Limited Proteolysis Mass Spectrometry.

Therapeutic proteins are commonly conjugated with polymers to modulate their pharmacokinetics but often lack a description of the polymer-protein interaction. We deployed limited proteolysis mass spectrometry (LiP-MS) to reveal the interaction of polyethylene glycol (PEG) and PEG alternative polymers with interferon-α2a (IFN). Target conjugates were digested with the specific protease trypsin and a "heavy" N-IFN wild type (IFN-WT) for time-resolved quantification of the cleavage dynamics.

Polyethyleneimine-Based Cryogels Enabling the Selective and Reversible Adsorption of Chlorine.

Herein hyperbranched polyethyleneimine (hPEI) cryogels are reported for the selective and reversible adsorption of elemental chlorine. The cryogels are prepared in an aqueous solution by crosslinking with glutaraldehyde at subzero temperatures. The final macroporous composites bearing ammonium chloride groups are obtained after freeze-drying.

Self-Assembly of a Perfluorinated Amphiphilic Cyanine Dye into Branched Tubular J-Aggregates.

The self-assembly process is governed by the individual constituents of molecules through precise non-covalent interactions. Amphiphilic cyanines are intriguing in supramolecular chemistry due to the large polarizability of their delocalized π-electron systems, their tuneable optical properties and their ability to form well-defined self-assembled structures in different media. Here we present the synthesis of a novel tetrahydroxy amphiphilic carbocyanine dye with perfluoro alkylated chains -(CH)-(CF)-CF as hydrophobic segments and aminoproanediol as hydrophilic segment.

Sulfated Cellulose Nanofiber Hydrogel with Mucus-Like Activities for Virus Inhibition.

Mucus is the first defense barrier against viruses in the human immune system. Inspired by the mucus structure, we designed a highly sulfated hydrogel to bind viruses and prevent infection of the underlying cells. The hydrogel was formed by gelation of sulfated cellulose nanofiber (SCNF) with Ca.

Redox-Responsive Hydrogels Loaded with an Antibacterial Peptide as Controlled Drug Delivery for Healing Infectious Wounds.

Infectious wounds occur when harmful microorganisms such as bacteria or viruses invade a wound site. Its problems associated include delayed healing, increased pain, swelling, and the potential for systemic infections. Therefore, developing new wound dressing materials with antibacterial effects is crucial for improving the healing process.

Polyglycerol-Shelled Reduction-Sensitive Polymersome for DM1 Delivery to HER-2-Positive Breast Cancer.

Supramolecular delivery systems with the prolonged circulation, the potential for diverse functionalization, and few toxin-related limitations have been extensively studied. For the present study, we constructed a linear polyglycerol-shelled polymersome attached with the anti-HER-2-antibody trastuzumab. We then covalently loaded the anticancer drug DM1 in the polymersome via dynamic disulfide bonding.

Biomaterial-based sponge for efficient and environmentally sound removal of bacteria from water.

Designing materials capable of disinfecting water without releasing harmful by-products is an ongoing challenge. Here, we report a novel polycationic sponge material synthesized from chitosan derivatives and cellulose fibers, exhibiting antibacterial properties. The design of such material is based on three key principles.

Mucus-Inspired Self-Healing Hydrogels: A Protective Barrier for Cells against Viral Infection.

Mucus is a dynamic biological hydrogel, composed primarily of the glycoprotein mucin, exhibits unique biophysical properties and forms a barrier protecting cells against a broad-spectrum of viruses. Here, this work develops a polyglycerol sulfate-based dendronized mucin-inspired copolymer (MICP-1) with ≈10% repeating units of activated disulfide as cross-linking sites. Cryo-electron microscopy (Cryo-EM) analysis of MICP-1 reveals an elongated single-chain fiber morphology.

Mucin-Inspired Polymeric Fibers for Herpes Simplex Virus Type 1 Inhibition.

Mucus lines the epithelial cells at the biological interface and is the first line of defense against multiple viral infections. Mucins, the gel-forming components of mucus, are high molecular weight glycoproteins and crucial for preventing infections by binding pathogens. Consequently, mimicking mucins is a promising strategy for new synthetic virus inhibitors.

Post-Radiotherapy Dysphagia in Head and Neck Cancer: Current Management by Speech-Language Pathologists.

Dysphagia, difficulty in eating and drinking, remains the most common side effect of radiotherapy treatment for head and neck cancer (HNC) with devastating consequences for function and quality of life (QOL). Over the past decade, 5-year survival has improved due to multiple factors including treatment advances, reduction in smoking, introduction of the human papillomavirus (HPV) vaccine and more favourable prognosis of HPV-related cancers. Increased prevalence of HPV-positive disease, which tends to affect younger individuals, has led to an elevated number of people living for longer with the sequelae of cancer and its treatment.

Topical Delivery of Tofacitinib in Dermatology: The Promise of a Novel Therapeutic Class Using Biodegradable Dendritic Polyglycerol Sulfates.

Inflammatory skin diseases, such as psoriasis, atopic dermatitis, and alopecia areata, occur when the regulatory tolerance of the innate immune system is disrupted, resulting in the activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory signaling pathway by interleukin 6 (IL-6) and other key inflammatory cytokines. JAK inhibitors, such as tofacitinib, bind to these enzymes which are coupled to receptors on cell surfaces and block the transcription of inflammatory cytokine-induced genes. The first topical applications are being marketed, yet insufficient effects regarding indications, such as alopecia areata, suggest that improved delivery technologies could help increase the efficacy.

Photo-responsive hydrogels based on a ruthenium complex: synthesis and degradation.

We report the synthesis of a photo responsive metallo-hydrogel based on a ruthenium(II) complex as a functional cross-linker. This metal complex contains reactive 4AAMP (= 4-(acrylamidomethyl)pyridine) ligands, which can be cleaved by light-induced ligand substitution. Ru[(bpy)(4AAMP)] cross-links 4-arm-PEG-SH macromonomers by thia-Michael-addition to the photocleavable 4AAMP ligand for the preparation of the hydrogel.

Synthesis of -symmetric star shaped amphiphiles for drug delivery applications.

-symmetric star-shaped aromatic compounds are known to possess unique characteristics which facilitate their industrial and biomedical applications. Herein, we report the design, synthesis, self-assembly and drug/dye delivery capabilities of -symmetric, hexa-substituted benzene-based amphiphiles. The synthesis of the hexa-substituted -symmetric core involves -acetylation of phloroglucinol to yield the corresponding tri-acetyl derivative.

Corelease of Genotoxic Polycyclic Aromatic Hydrocarbons and Nanoparticles from a Commercial Aircraft Jet Engine - Dependence on Fuel and Thrust.

Jet engines are important contributors to global CO emissions and release enormous numbers of ultrafine particles into different layers of the atmosphere. As a result, aviation emissions are affecting atmospheric chemistry and promote contrail and cloud formation with impacts on earth's radiative balance and climate. Furthermore, the corelease of nanoparticles together with carcinogenic polycyclic aromatic hydrocarbons (PAHs) affects air quality at airports.

Power of the Disulfide Bond: An Ideal Random Copolymerization of Biodegradable Redox-Responsive Hyperbranched Polyglycerols.

The development of copolymerization techniques that can randomly incorporate biodegradable moieties into the hyperbranched polyglycerol backbone is an option to prevent its bioaccumulation in vivo. In this study, redox-responsive and biocompatible hyperbranched polyglycerol copolymers of glycidol and 1,4,5-oxadithiepan-2-one were synthesized with an adjustable molecular weight and a defined disulfide bond content through anionic and coordination-insertion ring-opening polymerization. A truly random incorporation of the monomers was achieved under both copolymerization mechanisms.

Esterase-Responsive Polyglycerol-Based Nanogels for Intracellular Drug Delivery in Rare Gastrointestinal Stromal Tumors.

Rare gastrointestinal stromal tumors (GISTs) are caused by mutations in the KIT and PDGFRA genes. Avapritinib (BLU-285) is a targeted selective inhibitor for mutated KIT and PDGFRA receptors that can be used to treat these tumors. However, there are subtypes of GISTs that exhibit resistance against BLU-285 and thus require other treatment strategies.

2D and 3D Micropatterning of Mussel-Inspired Functional Materials by Direct Laser Writing.

This work addresses the critical need for multifunctional materials and substrate-independent high-precision surface modification techniques that are essential for advancing microdevices and sensing elements. To overcome existing limitations, the versatility of mussel-inspired materials (MIMs) is combined with state-of-the-art multiphoton direct laser writing (DLW) microfabrication. In this way, 2D and 3D MIM microstructures of complex designs are demonstrated with sub-micron to micron resolution and extensive post-functionalization capabilities.

Sulfated Polyglycerol-Modified Hydrogels for Binding HSV-1 and RSV.

Heparan sulfate (HS) is a highly sulfated polysaccharide on the surface of mammalian cells and in the extracellular matrix and has been found to be important for virus binding and infection. In this work, we designed synthetic hydrogels with viral binding and deactivation activities through the postfunctionalization of an HS-mimicking polyelectrolyte and alkyl chains. Three polyglycerol-based hydrogels were prepared as substrates and postfunctionalized by sulfated linear polyglycerol (lPGS) via thiol-ene click reaction.