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Amino acid-based poly(ester urea)s are an attractive class of polymers that are of interest for a variety of biomedical applications. Generally, amino acid-based poly(ester urea)s are prepared by polymerization of diamines, which are obtained from the corresponding amino acids and aliphatic diols. This article presents an alternative synthetic strategy that uses diamine monomers obtained from aromatic, 4-hydroxycinnamic acid-derived diols. A library of structurally related diamine monomers has been prepared by coupling l-leucine to 4-hydroxycinnamic acid-based diols that incorporate alkyl spacers of different lengths. The exploration of 4-hydroxycinnamic acid as a building block is interesting as it can be obtained from various biological resources, such as for example lignin, and thus provides an opportunity to take advantage of (under-utilized) bio-based renewables for the design of new polymer materials. These diamine monomers can be copolymerized in a solvent-free, one-pot, two-step process using dimethyl carbonate as an environmentally sustainable reagent to afford amino acid-based aromatic poly(ester urea) homo- and copolymers with thermal properties that can be tuned by varying the chemical structure of the diamine monomer, or via copolymerization of two different monomers., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

Upon exposure to a good solvent, polymer brushes prepared via surface-initiated polymerization can undergo degrafting via cleavage of bonds that anchor the polymer tethers to the underlying substrate. As polymer brushes are often used in a solvent swollen state, this has implications for the longevity of these polymer coatings. Improving the fundamental understanding of this process is thus also of practical importance. It is believed that degrafting is the consequence of tension amplification at the bonds that anchor the polymer grafts, which is driven by swelling of the polymer brush film. Taking advantage of the sensitivity of the swelling behavior of poly(3-sulfopropyl methacrylate) (PSPMA) brushes toward changes in ionic strength, this study has investigated the degrafting behavior of these brushes in aqueous media at different LiCl and NaCl concentrations. The aim of these experiments was to investigate whether the rate constant of the degrafting process was correlated with the swelling ratio of the PSPMA brushes. The experiments show that in aqueous LiCl solutions, the initial rate constant of the degrafting process is correlated with the swelling ratio of the PSPMA brush. This observation represents a first example of the correlation between these two parameters for hydrophilic polymer brushes in aqueous media and supports the idea that degrafting is a mechanochemical process driven by a swelling-induced tension at the polymer-substrate interface.

Ought to their bioinert properties and facile synthesis, poly[(oligoethylene glycol)methacrylate]s (POEGMAs) have been raised as attractive alternatives to poly(ethylene glycols) (PEGs) in an array of (bio)material applications, especially when they are applied as polymer brush coatings. However, commercially available OEG-methacrylate (macro)monomers feature a broad distribution of OEG lengths, thus generating structurally polydisperse POEGMAs when polymerized through reversible deactivation radical polymerization. Here, we demonstrate that the interfacial physicochemical properties of POEGMA brushes are significantly affected by their structural dispersity, i.e. , the degree of heterogeneity in the length of side OEG segments. POEGMA brushes synthesized from discrete (macro)monomers obtained through chromatographic purification of commercial mixtures show increased hydration and reduced adhesion when compared to their structurally polydisperse analogues. The observed alteration of interfacial properties is directly linked to the presence of monodisperse OEG side chains, which hamper intramolecular and intermolecular hydrophobic interactions while simultaneously promoting the association of water molecules. These phenomena provide structurally homogeneous POEGMA brushes with a more lubricious and protein repellent character with respect to their heterogeneous counterparts. More generally, in contrast to what has been assumed until now, the properties of POEGMA brushes cannot be anticipated while ruling out the effect of dispersity by (macro)monomer feeds. Simultaneously, side chain dispersity of POEGMAs emerges as a critical parameter for determining the interfacial characteristics of brushes.

Piezo- and pyroelectric materials are of interest, for example, for energy harvesting applications, for the development of tactile sensors, as well as neuromorphic computing. This study reports the observation of pyro- and piezoelectricity in thin surface-attached polymer brushes containing zwitterionic and electrolytic side groups that are prepared via surface-initiated polymerization. The pyro- and piezoelectric properties of the surface-grafted polyelectrolyte brushes are found to sensitively depend on and can be tuned by variation of the counterion. The observed piezo- and pyroelectric properties reflect the structural complexity of polymer brushes, and are attributed to a complex interplay of the non-uniform segment density within these films, together with a non-uniform distribution of counterions and specific ion effects. The fabrication of thin pyroelectric films by surface-initiated polymerization is an important addition to the existing strategies toward such materials. Surface-initiated polymerization, in particular, allows for facile grafting of polar thin polymer films from a wide range of substrates via a straightforward two-step protocol that obviates the need for multistep laborious synthetic procedures or thin film deposition protocols. The ability to produce polymer brushes with piezo- and pyroelectric properties opens up new avenues of application of these materials, for example, in energy harvesting or biosensing., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

The preparation of polymer gels via cross-linking of four-arm star-shaped poly(ethylene glycol) (Tetra-PEG) precursors is an attractive strategy to prepare networks with relatively well-defined topologies. Typically, Tetra-PEG gels are obtained by cross-linking heterocomplementary reactive Tetra-PEG precursors. This study, in contrast, explores the cross-linking of self-reactive, thiol-end functional Tetra-PEG macromers to form disulfide-cross-linked gels. The structure of the disulfide-cross-linked Tetra-PEG gels was studied with multiple-quantum NMR (MQ-NMR) spectroscopy and small-angle neutron scattering (SANS) experiments. In line with earlier simulation studies, these experiments showed a strong dependence of the relative fractions of the different network connectivities on the concentration of the thiol-end functional Tetra-PEG macromer that was used for the synthesis of the networks. Disulfide-cross-linked Tetra-PEG gels prepared at macromer concentrations below the overlap concentration ( c = 0.66 c *) primarily feature defect connectivity motifs, such as primary loops and dangling ends. For networks prepared at macromer concentrations above the overlap concentration, the fraction of single-link connectivities was found to be similar to that in amide-cross-linked Tetra-PEG gels obtained by heterocomplementary cross-linking of N -hydroxysuccinimide ester and amine functional Tetra-PEG macromers. Since disulfide bonds are susceptible to reductive cleavage, these disulfide-cross-linked gels are of interest, e.g., as reduction-sensitive hydrogels for a variety of biomedical applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In the context of transitioning toward a more sustainable use of natural resources, the application of lignin to substitute commonly utilized petroleum-based plastics can play a key role. Although lignin is highly available at low cost and presents interesting properties, such as antioxidant and UV barrier activities, its application is limited by its low reactivity, which is a consequence of harsh conditions normally used to extract lignin from biomass. In this work, the use of glyoxylic acid lignin (GA lignin), rich in carboxylic acid groups and hence highly reactive toward epoxy cross-linkers, is presented. GA lignin, which is directly extracted from biomass via a one-step aldehyde-assisted fractionation process, allowed the preparation of thermoset films and coatings via a simple reaction with sustainable poly(ethylene glycol) diglycidyl ether and glycerol diglycidyl ether cross-linkers. This allows one to prepare freestanding films containing up to 70 wt % lignin with tunable mechanical properties and covalently surface-attached coatings containing up to 90 wt % lignin with high solvent resistance. Both films and coatings display antioxidant properties and combine excellent UV barrier activity with high visible transparency, which is attractive for applications in sustainable food packaging., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Polymer brushes are densely grafted, chain end-tethered assemblies of polymers that can be produced via surface-initiated polymerization. Typically, this is accomplished using initiators or chain transfer agents that are covalently attached to the substrate. This manuscript reports an alternative route towards polymer brushes, which involves the use of non-covalent cucurbit[7]uril-adamantane host-guest interactions to surface-immobilize initiators for atom transfer radical polymerization. These non-covalent initiators can be used for the surface-initiated atom transfer radical polymerization of a variety of water-soluble methacrylate monomers to generate supramolecular polymer brushes with film thicknesses of more than 100 nm. The non-covalent nature of the initiator also allows facile access to patterned polymer brushes, which can be produced in straightforward fashion by drop-casting a solution of the initiator-modified guest molecules onto a substrate that presents the cucurbit[7]uril host., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Bacteria represent a class of living cells that are very attractive carriers for the transport and delivery of nano- and microsized particles. The use of cell-based carriers, such as for example bacteria, may allow to precisely direct nano- or microsized cargo to a desired site, which would greatly enhance the selectivity of drug delivery and allow to mitigate side effects. One key step towards the use of such nano-/microparticle - bacteria hybrids is the immobilization of the cargo on the bacterial cell surface. To fabricate bacteria - nano-/microparticle biohybrid microsystems, a wide range of chemical approaches are available that can be used to immobilize the particle payload on the bacterial cell surface. This article presents an overview of the various covalent and noncovalent chemistries that are available for the preparation of bacteria - nano-/microparticle hybrids. For each of the different chemical approaches, an overview will be presented that lists the bacterial strains that have been modified, the type and size of nanoparticles that have been immobilized, as well as the methods that have been used to characterize the nanoparticle-modified bacteria., (© 2022 Wiley-VCH GmbH.)

Anion-exchange-membrane fuel cells (AEMFCs) are a cost-effective alternative to proton-exchange-membrane fuel cells (PEMFCs). The development of high-performance and durable AEMFCs requires highly conductive and robust anion-exchange membranes (AEMs). However, AEMs generally exhibit a trade-off between conductivity and dimensional stability. Here, a fluorination strategy to create a phase-separated morphological structure in poly(aryl piperidinium) AEMs is reported. The highly hydrophobic perfluoroalkyl side chains augment phase separation to construct interconnected hydrophilic channels for anion transport. As a result, these fluorinated PAP (FPAP) AEMs simultaneously possess high conductivity (>150 mS cm -1 at 80 °C) and high dimensional stability (swelling ratio <20% at 80 °C), excellent mechanical properties (tensile strength >80 MPa and elongation at break >40%) and chemical stability (>2000 h in 3 m KOH at 80 °C). AEMFCs with a non-precious Co-Mn spinel cathode using the present FPAP AEMs achieve an outstanding peak power density of 1.31 W cm -2 . The AEMs remain stable over 500 h of fuel cell operation at a constant current density of 0.2 A cm -2 ., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Swelling in polymer materials is a ubiquitous phenomenon. At a molecular level, swelling is dictated by solvent-polymer interactions, and has been thoroughly studied both theoretically and experimentally. Favorable solvent-polymer interactions result in the solvation of polymer chains. For polymers in confined geometries, such as those that are tethered to surfaces, or for polymer networks, solvation can lead to swelling-induced tensions. These tensions act on polymer chains and can lead to stretching, bending, or deformation of the material both at the micro- and macroscopic scale. This Invited Feature Article sheds light on such swelling-induced mechanochemical phenomena in polymer materials across dimensions, and discusses approaches to visualize and characterize these effects.

The exploration of renewable resources is essential to help transition toward a more sustainable materials economy. The valorization of lignin can be a key component of this transition. Lignin is an aromatic polymer that constitutes approximately one-third of the total lignocellulosic biomass and is isolated in huge quantities as a waste material of biofuel and paper production. About 98% of the 100 million tons of lignin produced each year is simply burned as low-value fuel, so this renewable polymer is widely available at very low cost. Lignin has valuable properties that make it a promising material for numerous applications, but it is far from being fully exploited. The aim of this Perspective is to highlight opportunities and challenges for the use of lignin-based materials in food packaging, antimicrobial, and agricultural applications. In the first part, the ongoing research and the possible future developments for the use of lignin as an additive to improve mechanical, gas and UV barrier, and antioxidant properties of food packaging items will be treated. Second, the application of lignin as an antimicrobial agent will be discussed to elaborate on the activity of lignin against bacteria, fungi, and viruses. Finally, the use of lignin in agriculture will be presented by focusing on the application of lignin as fertilizer.

Polymer brushes are thin polymer films that consist of densely grafted, chain-end tethered polymers. These thin polymer films can be produced either by anchoring presynthesized chain-end functional polymers to the surface of interest ("grafting to"), or by using appropriately modified surfaces to facilitate growth of polymer chains from the substrate ("grafting from"). The vast majority of polymer brushes that have been prepared and studied so far involved chain-end tethered polymer assemblies that are anchored to the surface via covalent bonds. In contrast, the use of noncovalent interactions to prepare chain-end tethered polymer thin films is much less explored. Anchoring or growing polymer chains using noncovalent interactions results in supramolecular polymer brushes. Supramolecular polymer brushes may possess unique chain dynamics as opposed to their covalently tethered counterparts, which could provide avenues to, for example, renewable or (self-)healable surface coatings. This Perspective article provides an overview of the various approaches that have been used so far to prepare supramolecular polymer brushes. After presenting an overview of the various approaches that have been used to prepare supramolecular brushes via the "grafting to" strategy, examples will be presented of strategies that have been successfully applied to produce supramolecular polymer brushes via "grafting from" methods., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Transmission of viruses through contact with contaminated surfaces is an important pathway for the spread of infections. Antiviral surface coatings are useful to minimize such risks. Current state-of-the-art approaches toward antiviral surface coatings either involve metal-based materials or complex synthetic polymers. These approaches, however, even if successful, will have to face great challenges when it comes to large-scale applications and their environmental sustainability. Here, an antiviral surface coating was prepared by spin-coating lignin, a natural biomass residue of the paper production industry. We show effective inactivation of herpes simplex virus type 2 (>99% after 30 min) on a surface coating that is low-cost and environmentally sustainable. The antiviral mechanism of the lignin surface was investigated and is attributed to reactive oxygen species generated upon oxidation of lignin phenols. This mechanism does not consume the surface coating (as opposed to the release of a specific antiviral agent) and does not require regeneration. The coating is stable in ambient conditions, as demonstrated in a 6 month aging study that did not reveal any decrease in antiviral activity. This research suggests that natural compounds may be used for the development of affordable and sustainable antiviral coatings., Competing Interests: The authors declare the following competing financial interest(s): S.B. and J.S.L. are inventors on a European patent application (EP19202957) that was submitted by EPFL and covers the isolation of different functionalized lignins via the aldehyde assisted fractionation process. J.S.L. is co-founder and part owner of Bloom Biorenewables Ltd that aims at commercializing the aldehyde assisted fractionation process., (© 2022 The Authors. Published by American Chemical Society.)

The development of sustainable plastics from abundant renewable feedstocks has been limited by the complexity and efficiency of their production, as well as their lack of competitive material properties. Here we demonstrate the direct transformation of the hemicellulosic fraction of non-edible biomass into a tricyclic diester plastic precursor at 83% yield (95% from commercial xylose) during integrated plant fractionation with glyoxylic acid. Melt polycondensation of the resulting diester with a range of aliphatic diols led to amorphous polyesters (M n  = 30-60 kDa) with high glass transition temperatures (72-100 °C), tough mechanical properties (ultimate tensile strengths of 63-77 MPa, tensile moduli of 2,000-2,500 MPa and elongations at break of 50-80%) and strong gas barriers (oxygen transmission rates (100 µm) of 11-24 cc m -2  day -1  bar -1 and water vapour transmission rates (100 µm) of 25-36 g m -2  day -1 ) that could be processed by injection moulding, thermoforming, twin-screw extrusion and three-dimensional printing. Although standardized biodegradation studies still need to be performed, the inherently degradable nature of these materials facilitated their chemical recycling via methanolysis at 64 °C, and eventual depolymerization in room-temperature water., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Poly(lactic acid) (PLA) represents one of the most widely used biodegradable polymers for food packaging applications. While this material provides many advantages, it is characterized by limited antioxidant and UV-barrier properties. Blending PLA with lignin is an attractive strategy to address these limitations. Lignin possesses antioxidant properties and absorbs UV-light and is a widely available low value byproduct of the paper and pulp industry. This study has explored the use of lignin nanoparticles to augment the properties of PLA-based films. A central challenge in the preparation of PLA-lignin nanoparticle blend films is to avoid nanoparticle aggregation, which could compromise optical properties as well as antioxidant activity, among others. To avoid nanoparticle aggregation in the PLA matrix, PLA-grafted lignin nanoparticles were prepared via organocatalyzed lactide ring-opening polymerization. In contrast to lignin and unmodified lignin nanoparticles, these PLA-grafted lignin nanoparticles could be uniformly dispersed in PLA for lignin contents up to 10 wt %. The addition of as little as the equivalent of 1 wt % of lignin of these nanoparticles effectively blocked transmission of 280 nm UV-light. At the same time, these blend films retained reasonable visible light transmittance. The optical properties of the PLA lignin blend films also benefited from the well-dispersed nature of the PLA-grafted nanoparticles, as evidenced by significantly higher visible light transmittance of blends of PLA and PLA-grafted nanoparticles, as compared to blends prepared from PLA with lignin or unmodified lignin nanoparticles. Finally, blending PLA with PLA-grafted lignin nanoparticles greatly augments the antioxidant activity of these films., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Anion-exchange membrane fuel cells (AEMFCs) are a promising, next-generation fuel cell technology. AEMFCs require highly conductive and robust anion-exchange membranes (AEMs), which are challenging to develop due to the tradeoff between conductivity and water uptake. Here we report a method to prepare high-molecular-weight branched poly(aryl piperidinium) AEMs. We show that branching reduces water uptake, leading to improved dimensional stability. The optimized membrane, b-PTP-2.5, exhibits simultaneously high OH - conductivity (>145 mS cm -1 at 80 °C), high mechanical strength and dimensional stability, good processability, and excellent alkaline stability (>1500 h) in 1 M KOH at 80 °C. AEMFCs based on b-PTP-2.5 reached peak power densities of 2.3 W cm -2 in H 2 -O 2 and 1.3 W cm -2 in H 2 -air at 80 °C. The AEMFCs can run stably under a constant current of 0.2 A cm -2 over 500 h, during which the b-PTP-2.5 membrane remains stable., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Cancer vaccination is a powerful strategy to combat cancer. A very attractive approach to prime the immune system against cancer cells involves the use of tumor lysate as antigen source. The immunogenicity of tumor lysate can be further enhanced by treatment with hypochlorous acid. This study explores poly(lactic-co-glycolic acid) (PLGA) nanoparticles to enhance the delivery of oxidized tumor lysate to dendritic cells. Using human donor-derived dendritic cells, it is found that the use of PLGA nanoparticles enhances antigen uptake and dendritic cell maturation, as compared to the use of the free tumor lysate. The ability of the activated dendritic cells to stimulate autologous peripheral blood mononuclear cells (PBMCs) is assessed in vitro by coculturing PBMCs with A375 melanoma cells. Live cell imaging analysis of this experiment highlights the potential of nanoparticle-mediated dendritic-cell-based vaccination approaches. Finally, the efficacy of the PLGA nanoparticle formulation is evaluated in vivo in a therapeutic vaccination study using B16F10 tumor-bearing C57BL/6J mice. Animals that are challenged with the polymer nanoparticle-based oxidized tumor lysate formulation survive for up to 50 days, in contrast to a maximum of 41 days for the group that receives the corresponding free oxidized tumor lysate-based vaccine., (© 2021 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

Peptides and proteins represent an emerging class of powerful therapeutics. Peptide and protein nanogels are attractive carriers for the transport and delivery of biologically active peptides and proteins because they allow essentially quantitative encapsulation of these biologics. One interesting field of use of peptide and protein nanogels is the transport of antigens and adjuvants in cancer immunotherapy. This study demonstrates the use of reduction-sensitive protein nanogels for the delivery of ovalbumin and oxidized tumor lysate-based antigens to mouse and human-donor-derived dendritic cells. Challenging mouse-derived and human dendritic cells with reduction-sensitive ovalbumin nanogels was found to significantly enhance antigen uptake as compared to the use of the corresponding free protein antigen. The experiments with mouse-derived dendritic cells further showed that the administration of ovalbumin in the form of reduction-sensitive nanogels enhanced dendritic cell maturation as well as the presentation of the SIINFEKL epitope as compared to experiments that use free ovalbumin. In addition to ovalbumin as a model antigen, the feasibility of reduction-sensitive nanogels was also demonstrated for the delivery of oxidized, whole tumor lysate-based cancer antigens. In experiments with dendritic cells harvested from human donors, dendritic cell uptake of the oxidized tumor lysate antigen was significantly enhanced in experiments that used oxidized tumor lysate nanogels as compared to the free antigen.

Surface-initiated polymerization reactions are a powerful tool to generate chain-end-tethered polymer brushes. This report presents a synthetic strategy that gives access to structurally well-defined hydrocarbon polymer brushes of controlled molecular weights, which can be further modified to generate more complex surface-attached polymer architectures. The hydrocarbon brushes reported in this study are polymethylene brushes that are obtained via surface-initiated C1 polyhomologation of dimethylsulfoxonium methylide. The strategy outlined here is based on the use of an alkylboronic acid pinacol ester initiator, which allows for controlled, unidirectional chain growth by monomer insertion into only the C-B bond of the initiator and which presents the polymerization active group at the growing polymer chain end. This surface-initiated C1 polyhomologation methodology is compatible with photopatterning strategies and can be used to generate micropatterned polymethylene brush films. Furthermore, conversion of the boronic ester chain-end functionalities to hydroxyl groups allows for selective chain-end modification and enables access to a variety of surface-anchored block copolymer architectures by chain extension via, for example, ring-opening or atom transfer radical polymerization chemistries.

Cells are attractive as carriers that can help to enhance control over the biodistribution of polymer nanomedicines. One strategy to use cells as carriers is based on the cell surface immobilization of the nanoparticle cargo. While a range of strategies can be used to immobilize nanoparticles on cell surfaces, only limited effort has been made to investigate the effect of these surface modification chemistries on cell viability and functional properties. This study has explored seven different approaches for the immobilization of poly(lactic acid) (PLA) nanoparticles on the surface of two different T lymphocyte cell lines. The cell lines used were human Jurkat T cells and CD4 + T EM cells. The latter cells possess blood-brain barrier (BBB) migratory properties and are attractive for the development of cell-based delivery systems to the central nervous system (CNS). PLA nanoparticles were immobilized either via covalent active ester-amine, azide-alkyne cycloaddition, and thiol-maleimide coupling, or via noncovalent approaches that use lectin-carbohydrate, electrostatic, or biotin-NeutrAvidin interactions. The cell surface immobilization of the nanoparticles was monitored with flow cytometry and confocal microscopy. By tuning the initial nanoparticle/cell ratio, T cells can be decorated with up to ∼185 nanoparticles/cell as determined by confocal microscopy. The functional properties of the nanoparticle-decorated cells were assessed by evaluating their binding to ICAM-1, a key protein involved in the adhesion of CD4 + T EM cells to the BBB endothelium, as well as in a two-chamber model in vitro BBB migration assay. It was found that the migratory behavior of CD4 + T EM cells carrying carboxylic acid-, biotin-, or Wheat germ agglutinin (WGA)-functionalized nanoparticles was not affected by the presence of the nanoparticle payload. In contrast, however, for cells decorated with maleimide-functionalized nanoparticles, a reduction in the number of migratory cells compared to the nonmodified control cells was observed. Investigating and understanding the impact of nanoparticle-cell surface conjugation chemistries on the viability and properties of cells is important to further improve the design of cell-based nanoparticle delivery systems. The results of this study present a first step in this direction and provide first guidelines for the surface modification of T cells, in particular in view of their possible use for drug delivery to the CNS.

Protein-polymer conjugates are a class of molecules that combine the stability of polymers with the diversity, specificity, and functionality of biomolecules. These bioconjugates can result in hybrid materials that display properties not found in their individual components and can be particularly relevant for drug delivery applications. Engineering amphiphilicity into these bioconjugate materials can lead to phase separation and the assembly of high-order structures. The assembly, termed self-assembly, of these hierarchical structures entails multiple levels of organization: at each level, new properties emerge, which are, in turn, influenced by lower levels. Here, we provide a critical review of protein-polymer conjugate self-assembly and how these materials can be used for therapeutic applications and drug delivery. In addition, we discuss central bioconjugate design questions and propose future perspectives for the field of protein-polymer conjugate self-assembly., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Developing molecules that emulate the properties of naturally occurring ice-binding proteins (IBPs) is a daunting challenge. Rather than relying on the (limited) existing structure-property relationships that have been established for IBPs, here we report the use of phage display for the identification of short peptide mimics of IBPs. To this end, an ice-affinity selection protocol is developed, which enables the selection of a cyclic ice-binding peptide containing just 14 amino acids. Mutational analysis identifies three residues, Asp8, Thr10 and Thr14, which are found to be essential for ice binding. Molecular dynamics simulations reveal that the side chain of Thr10 hydrophobically binds to ice revealing a potential mechanism. To demonstrate the biotechnological potential of this peptide, it is expressed as a fusion ('Ice-Tag') with mCherry and used to purify proteins directly from cell lysate.

Cells are powerful carriers that can help to improve the delivery of nanomedicines. One approach to use cells as carriers is to immobilize the nanoparticulate cargo on the cell surface. While a plethora of chemical conjugation strategies are available to bind nanoparticles to cell surfaces, only relatively little is known about the effects of particle size and cell type on the surface immobilization of nanoparticles. This study investigates the biotin-NeutrAvidin mediated immobilization of model polymer nanoparticles with sizes ranging from 40 nm to 1 μm on two different T cell lines, viz., human Jurkat cells as well as mouse SJL/PLP7 T cells, which are of potential interest for drug delivery across the blood-brain barrier. The nanoparticle cell surface immobilization and the particle surface concentration and distribution were analyzed by flow cytometry and confocal microscopy. The functional properties of nanoparticle-modified SJL/PLP7 T cells were assessed in an ICAM-1 binding assay as well as in a two-chamber setup in which the migration of the particle-modified T cells across an in vitro model of the blood-brain barrier was studied. The results of these experiments highlight the effects of particle size and cell line on the surface immobilization of nanoparticles on living cells.

Cells are promising as carriers that can enhance the delivery of nanomedicines. Cells that carry nanomedicinal cargo, either immobilized on the cell surface or internalized, can allow for highly specific delivery and can enable the transport of nanomedicines across challenging physiological barriers. The effective use of cells as carriers for the transport and delivery of nanomedines requires a careful selection of the chemical strategies that are used to load the cell-based carriers with their cargo. To this end, an in-depth understanding of the impact of various cell-surface modification chemistries on the viability and functional properties of the cells is essential, and techniques are needed that allow characterization of nanoparticle-modified living cells. This article touches upon both of these aspects. The first part of this review will present an overview of contemporary strategies that are available for the cell surface immobilization of nanoparticle cargo. After that, the various techniques that are most frequently used for the characterization of nanoparticle-modified cells will be discussed.

Cells are attractive carriers for the transport and delivery of nanoparticulate cargo. The use of cell-based carriers allows one to enhance control over the biodistribution of drug-loaded polymers and polymer nanoparticles. One key element in the development of cell-based delivery systems is the loading of the cell-based carrier with the nanoparticle cargo, which can be achieved either by internalization of the payload or by immobilization on the cell surface. The surface modification of cells with nanoparticles or the internalization of nanoparticles by cells is usually monitored with fluorescence-based techniques, such as flow cytometry and confocal microscopy. In spite of the widespread use of these techniques, the use of fluorescent labels also poses some risks and has several drawbacks. Fluorescent dyes may bleach, or leach from, the nanoparticles or alter the physicochemical properties of nanoparticles and their interactions with and uptake by cells. Using poly(d,l-lactic acid) nanoparticles that are loaded with Coumarin 6, BODIPY 493/503, or DiO dyes as a model system, this paper demonstrates that the use of physically entrapped fluorescent labels can lead to false negative or erroneous results. The use of nanoparticles that contain covalently tethered fluorescent dyes instead was found to provide a robust approach to monitor cell surface conjugation reactions and to quantitatively analyze nanoparticle-decorated cells. Finally, it is shown that optical diffraction tomography is an attractive, alternative technique for the characterization of nanoparticle-decorated cells, which obviates the need for fluorescent labels.

Delivery of therapeutics to the central nervous system (CNS) is challenging due to the presence of the blood-brain barrier (BBB). Amongst various approaches that have been explored to facilitate drug delivery to the CNS, the use of cells that have the intrinsic ability to cross the BBB is relatively unexplored, yet very attractive. This paper presents a first proof-of-concept that demonstrates the feasibility of activated effector/memory CD4 + helper T cells (CD4 + T EM cells) as carriers for the delivery of polymer nanoparticles across the BBB. This study shows that CD4 + T EM cells can be decorated with poly(ethylene glycol)-modified polystyrene nanoparticles using thiol-maleimide coupling chemistry, resulting in the immobilization of ≈105 nanoparticles per cell as determined by confocal microscopy. The ability of these cells to serve as carriers to transport nanoparticles across the BBB is established in vitro and in vivo. Using in vitro BBB models, CD4 + T EM cells are found to be able to transport nanoparticles across the BBB both under static conditions as well as under physiological flow. Finally, upon systemic administration, nanoparticle-modified T cells are shown to enter the brain parenchyma of mice, demonstrating the brain delivery potential of this T cell subset in allogeneic hosts., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Rapid adhesion between tissue and synthetic materials is relevant to accelerate wound healing and to facilitate the integration of implantable medical devices. Most frequently, tissue adhesives are applied as a gel or a liquid formulation. This manuscript presents an alternative approach to mediate adhesion between synthetic surfaces and tissue. The strategy presented here is based on the modification of the surface of interest with a thin polymer film that can be transformed on-demand, using UV-light as a trigger, from a nonadhesive into a reactive and tissue adhesive state. As a first proof-of-concept, the feasibility of two photoreactive, thin polymer film platforms has been explored. Both of these films, colloquially referred to as polymer brushes, have been prepared using surface-initiated atom transfer radical polymerization (SI-ATRP) of 2-hydroxyethyl methacrylate (HEMA). In the first part of this study, it is shown that direct UV-light irradiation of PHEMA brushes generates tissue-reactive aldehyde groups and facilitates adhesion to meniscus tissue. While this strategy is very straightforward from an experimental point of view, a main drawback is that the generation of the tissue reactive aldehyde groups uses the 250 nm wavelength region of the UV spectrum, which simultaneously leads to extensive photodegradation of the polymer brush. The second part of this report outlines the synthesis of PHEMA brushes that are modified with 4-[3-(trifluoromethyl)-3 H -diazirin-3-yl]benzoic acid (TFMDA) moieties. UV-irradiation of the TFMDA containing brushes transforms the diazirine moieties into reactive carbenes that can insert into C-H, N-H, and O-H bonds and mediate the formation of covalent bonds between the brush surface and meniscus tissue. The advantage of the TFMDA-modified polymer brushes is that these can be activated with 365 nm wavelength UV light, which does not cause photodegradation of the polymer films. While the work presented in this manuscript has used silicon wafers and fused silica substrates as a first proof-of-concept, the versatility of SI-ATRP should enable the application of this strategy to a broad range of biomedically relevant surfaces.

Hydrophilic polymer brushes grown via surface-initiated polymerization from silicon oxide surfaces can detach or degraft in aqueous media. Degrafting of these chain end-tethered polymers is believed to involve hydrolysis of bonds at the polymer-substrate interface. Degrafting so far has not been reported for hydrophobic polymer brushes in non-aqueous media. This study has investigated the degrafting and swelling properties of poly(tert-butyl methacrylate) (PtBMA) brushes in different water-miscible, organic solvents, viz. DMF, acetone and THF. In the presence of a sufficient quantity of water in the organic solvent, degrafting was also observed for PtBMA brushes. More importantly, however, the rate of degrafting depended on the nature of the organic solvent and the apparent initial rate constant of the degrafting reaction was found to correlate with the swelling ratio of the polymer brush in the different solvents. This correlation is first, direct evidence in support of the hypothesis that degrafting is facilitated by a tension that acts on the bond(s) that tether the polymer chains to the surface and which is amplified upon swelling of the polymer brush., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mechanical stimuli are ubiquitous in the human body. In contrast to biochemical stimuli such as pH, redox, hypoxia or enzymes as well as exogenous stimuli such as magnetic fields, temperature or ultrasound, endogenous biomechanical stimuli have only received relatively limited attention as a means to trigger stimuli-sensitive materials. The aim of this short article is to highlight the potential of endogenous biomechanical stimuli to control the behaviour of biomaterials relevant to, for example, drug delivery or tissue repair and regeneration. This article will first provide an overview of the different biomechanical stimuli present at the cellular and tissue level in the human body. After that, examples from recent work will be presented that illustrate the use of biomechanical stimuli. This article ends with an outlook for future research.

Cellular uptake and intracellular trafficking of polymer conjugates or polymer nanoparticles is typically monitored using fluorescence-based techniques such as confocal microscopy. While these methods have provided a wealth of insight into the internalization and trafficking of polymers and polymer nanoparticles, they require fluorescent labeling of the polymer or polymer nanoparticle. Because in biological media fluorescent dyes may degrade, be cleaved from the polymer or particle, or even change uptake and trafficking pathways, there is an interest in fluorescent label-free methods to study the interactions between cells and polymer nanomedicines. This article presents a first proof-of-concept that demonstrates the feasibility of NanoSIMS to monitor the intracellular localization of polymer conjugates. For the experiments reported here, poly( N-(2-hydroxypropyl) methacrylamide)) (PHPMA) was selected as a prototypical polymer-drug conjugate. This PHPMA polymer contained a 19 F-label at the α-terminus, which was introduced in order to allow NanoSIMS analysis. Prior to the NanoSIMS experiments, the uptake and intracellular trafficking of the polymer was established using confocal microscopy and flow cytometry. These experiments not only provided detailed insight into the kinetics of these processes but were also important to select time points for the NanoSIMS analysis. For the NanoSIMS experiments, HeLa cells were investigated that had been exposed to the PHPMA polymer for a period of 4 or 15 h, which was known to lead to predominant lysosomal accumulation of the polymer. NanoSIMS analysis of resin-embedded and microtomed samples of the cells revealed a punctuated fluorine signal, which was found to colocalize with the sulfur signal that was attributed to the lysosomal compartments. The localization of the polymer in the endolysosomal compartments was confirmed by TEM analysis on the same cell samples. The results of this study illustrate the potential of NanoSIMS to study the uptake and intracellular trafficking of polymer nanomedicines.

The unique functionality of polyelectrolyte brushes depends on several types of specific interactions, including solvent structure effects, hydrophobic forces, electrostatic interactions, and specific ion interactions. Subtle variations in the solution environment can lead to conformational and surface structural changes of the polyelectrolyte brushes, which are mainly discussed from a surface-interaction perspective in this Focus Review. A brief overview is given of recent theoretical and experimental progress in the structure of polyelectrolyte brushes in various environments. Two important techniques for surface-force measurements are described, the surface forces apparatus (SFA) and atomic force microscopy (AFM), and some recent results on polyelectrolyte brushes are shown. Lastly, this Focus Review highlights the use of these surface-grafted polyelectrolyte brushes in the creation of functional surfaces for various applications, including nonfouling surfaces, boundary lubricants, and stimuli-responsive surfaces., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chain-end-labeled polymers are interesting for a range of applications. In polymer nanomedicine, chain-end-labeled polymers are useful to study and help understand cellular internalization and intracellular trafficking processes. The recent advent of fluorescent label-free techniques, such as nanoscale secondary ion mass spectrometry (NanoSIMS), provides access to high-resolution intracellular mapping that can complement information obtained using fluorescent-labeled materials and confocal microscopy and flow cytometry. Using poly( N -(2-hydroxypropyl)methacrylamide) (PHPMA) as a prototypical polymer nanomedicine, this paper presents a synthetic strategy to polymers that contain trace element labels, such as fluorine, which can be used for NanoSIMS analysis. The strategy presented in this paper is based on reversible addition fragmentation chain transfer (RAFT) polymerization of pentafluorophenyl methacrylate (PFMA) mediated by two novel chain-transfer agents (CTAs), which contain either one (α) or two (α,ω) fluorine labels. In the first part of this study, via a number of polymerization experiments, the polymerization properties of the fluorinated RAFT CTAs were established. 19 F NMR spectroscopy revealed that these fluorinated RAFT agents possess unique spectral signatures, which allow to directly monitor RAFT agent conversion and measure end-group fidelity. Comparison with 4-cyanopentanoic acid dithiobenzoate, which is a standard CTA for the RAFT polymerization of PFMA, revealed that the introduction of one or two fluorine labels does not significantly affect the polymerization properties of the CTA. In the last part of this paper, a proof-of-concept study is presented that demonstrates the feasibility of the fluorine-labeled poly(pentafluorophenyl methacrylate) polymers as platforms for the postpolymerization modification to generate PHPMA-based polymer nanomedicines., Competing Interests: The authors declare no competing financial interest.

Earth-abundant hydrogen evolution catalysts are essential for high-efficiency solar-driven water splitting. Although a significant amount of studies have been dedicated to the development of new catalytic materials, the microscopic assembly of these materials has not been widely investigated. Here, we describe an approach to control the three-dimensional (3D) assembly of amorphous molybdenum sulfide using polymer brushes as a template. To this end, poly(dimethylaminoethyl methacrylate) brushes were grown from highly oriented pyrolytic graphite. These cationic polymer films bind anionic MoS 4 2- through an anion-exchange reaction. In a final oxidation step, the polymer-bound MoS 4 2- is converted into the amorphous MoS x catalyst. The flexibility of the assembly design allowed systematic optimization of the 3D catalyst. The best system exhibited turnover frequencies up to 1.3 and 4.9 s -1 at overpotentials of 200 and 250 mV, respectively. This turnover frequency stands out among various molybdenum sulfide catalysts. The work demonstrates a novel strategy to control the assembly of hydrogen evolution reaction catalysts.

The clinical translation of protein drugs that act intracellularly is limited by the absence of safe and efficient intracellular protein delivery vehicles. Here, pH-sensitive coiled-coil peptide-cross-linked hyaluronic acid nanogels (HA-cNGs) were designed and investigated for targeted intracellular protein delivery to CD44 overexpressing MCF-7 breast cancer cells. HA-cNGs were obtained with a small size of 176 nm from an equivalent mixture of hyaluronic acid conjugates with GY(EIAALEK) 3 GC (E3) and GY(KIAALKE) 3 GC (K3) peptides, respectively, at pH 7.4 by nanoprecipitation. Circular dichroism (CD) proved the formation of coiled-coil structures between E3 and K3 peptides at pH 7.4 while fast uncoiling at pH 5.0. HA-cNGs showed facile loading of cytochrome C (CC) and greatly accelerated CC release under mild acidic conditions (18.4%, 76.8%, and 91.4% protein release in 24 h at pH 7.4, 6.0, and 5.0, respectively). Confocal microscopy and flow cytometry displayed efficient internalization of CC-loaded HA-cNGs and effective endosomal escape of CC in MCF-7 cancer cells. Remarkably, HA-cNGs loaded with saporin, a ribosome inactivating protein, exhibited significantly enhanced apoptotic activity to MCF-7 cells with a low IC 50 of 12.2 nM. These coiled-coil peptide-cross-linked hyaluronic acid nanogels have appeared as a simple and multifunctional platform for efficient intracellular protein delivery.