On the Road to Circular Polymer Brushes: Challenges and Prospects.

Polymer brushes are unique surface coatings that have been of high interest in research for the past decades due to their covalent tethering to surfaces and the broad spectrum of polymers that can be grafted to or grafted from various surfaces. Modification of surfaces with brushes may provide lubricious and/or antifouling properties, and they can also potentially be used in many application fields due to their high responsiveness toward certain stimuli. Generally, polymer brushes are long-lasting coatings, while their end-of-life has to date largely been neglected. Therefore, it is important to consider additional design methodologies to produce circular brushes, which will degrade after a certain period of time such that surfaces can be reused, and the potentially obtained monomers may be used again to synthesize new brushes. In this Perspective, we aim to tackle and understand the challenges to translate the knowledge on degradation and chemical recycling of bulk polymers toward circular polymer brushes. We summarized the recent developments on (bio)degradable polymer brushes and the challenges that are to be tackled toward their potential implementation as circular coatings.

Nanoscale Control of the Surface Functionality of Polymeric 2D Materials.

Typically, 2D nanosheets have a homogeneous surface, making them a major challenge to structure. This study proposes a novel concept of 2D organic nanosheets with a heterogeneously functionalized surface. This work achieves this by consecutively crystallizing two precisely synthesized polymers with different functional groups in the polymer backbone in a two-step process. First, the core platelet is formed and then the second polymer is crystallized around it. As a result, the central area of the platelets has a different surface functionality than the periphery. This concept offers two advantages: the resulting polymeric 2D platelets are stable in dispersion, which simplifies further processing and makes both crystal surfaces accessible for subsequent functionalization. Additionally, a wide variety of polymers can be used, making the process and the choice of surface functionalization very flexible.

Biobased Agents for Single-Particle Detection with Optoacoustics.

Optoacoustic (OA, photoacoustic) imaging synergistically combines rich optical contrast with the resolution of ultrasound within light-scattering biological tissues. Contrast agents have become essential to boost deep-tissue OA sensitivity and fully exploit the capabilities of state-of-the-art OA imaging systems, thus facilitating the clinical translation of this modality. Inorganic particles with sizes of several microns can also be individually localized and tracked, thus enabling new applications in drug delivery, microrobotics, or super-resolution imaging. However, significant concerns have been raised regarding the low bio-degradability and potential toxic effects of inorganic particles. Bio-based, biodegradable nano- and microcapsules consisting of an aqueous core with clinically-approved indocyanine green (ICG) and a cross-linked casein shell obtained in an inverse emulsion approach are introduced. The feasibility to provide contrast-enhanced in vivo OA imaging with nanocapsules as well as localizing and tracking individual larger microcapsules of 4-5 µm is demonstrated. All components of the developed capsules are safe for human use and the inverse emulsion approach is known to be compatible with a variety of shell materials and payloads. Hence, the enhanced OA imaging performance can be exploited in multiple biomedical studies and can open a route to clinical approval of agents detectable at a single-particle level.

Nanocarriers with Multiple Cargo Load-A Comprehensive Preparation Guideline Using Orthogonal Strategies.

Multifunctional nanocarriers enhance the treatment efficacy for modern therapeutics and have gained increasing importance in biomedical research. Codelivery of multiple bioactive molecules enables synergistic therapies. Coencapsulation of cargo molecules into one nanocarrier system is challenging due to different physicochemical properties of the cargo molecules. Additionally, coencapsulation of multiple molecules simultaneously shall proceed with high control and efficiency. Orthogonal approaches for the preparation of nanocarriers are essential to encapsulate sensitive bioactive molecules while preserving their bioactivity. Preparation of nanocarriers by physical processes (i.e., self-assembly or coacervation) and chemical reactions (i.e., click reactions, polymerizations, etc.) are considered as orthogonal methods to most cargo molecules. This review shall act as a guideline to allow the reader to select a suitable preparation protocol for a desired nanocarrier system. This article helps to select for combinations of cargo molecules (hydrophilic-hydrophobic, small-macro, organic-inorganic) with nanocarrier material and synthesis protocols. The focus of this article lies on the coencapsulation of multiple cargo molecules into biocompatible and biodegradable nanocarriers prepared by orthogonal strategies. With this toolbox, the selection of a preparation method for a known set of cargo molecules to prepare the desired biodegradable and loaded nanocarrier shall be provided.

Confining the Sol-Gel Reaction at the Water/Oil Interface: Creating Compartmentalized Enzymatic Nano-Organelles for Artificial Cells.

Living organisms compartmentalize their catalytic reactions in membranes for increased efficiency and selectivity. To mimic the organelles of eukaryotic cells, we develop a mild approach for in situ encapsulating enzymes in aqueous-core silica nanocapsules. In order to confine the sol-gel reaction at the water/oil interface of miniemulsion, we introduce an aminosilane to the silica precursors, which serves as both catalyst and an amphiphilic anchor that electrostatically assembles with negatively charged hydrolyzed alkoxysilanes at the interface. The semi-permeable shell protects enzymes from proteolytic attack, and allows the transport of reactants and products. The enzyme-carrying nanocapsules, as synthetic nano-organelles, are able to perform cascade reactions when enveloped in a polymer vesicle, mimicking the hierarchically compartmentalized reactions in eukaryotic cells. This in situ encapsulation approach provides a versatile platform for the delivery of biomacromolecules.

A circular dichroism study of the protective role of polyphosphoesters polymer chains in polyphosphoester-myoglobin conjugates.

Protein-polymer conjugates are a blooming class of hybrid systems with high biomedical potential. Despite a plethora of papers on their biomedical properties, the physical-chemical characterization of many protein-polymer conjugates is missing. Here, we evaluated the thermal stability of a set of fully-degradable polyphosphoester-protein conjugates by variable temperature circular dichroism, a common but powerful technique. We extensively describe their thermodynamic stability in different environments (in physiological buffer or in presence of chemical denaturants, e.g., acid or urea), highlighting the protective role of the polymer in preserving the protein from denaturation. For the first time, we propose a simple but effective protocol to achieve useful information on these systems in vitro, useful to screen new samples in their early stages.

RNA-Inspired and Accelerated Degradation of Polylactide in Seawater.

Marine plastic pollution is a worldwide challenge making advances in the field of biodegradable polymer materials necessary. Polylactide (PLA) is a promising biodegradable polymer used in various applications; however, it has a very slow seawater degradability. Herein, we present the first library of PLA derivatives with incorporated "breaking points" to vary the speed of degradation in artificial seawater from years to weeks. Inspired by the fast hydrolysis of ribonucleic acid (RNA) by intramolecular transesterification, we installed phosphoester breaking points with similar hydroxyethoxy side groups into the PLA backbone to accelerate chain scission. Sequence-controlled anionic ring-opening copolymerization of lactide and a cyclic phosphate allowed PLA to be prepared with controlled distances of the breaking points along the backbone. This general concept could be translated to other slowly degrading polymers and thereby be able to prevent additional marine pollution in the future.

Effect of Polymer Hydrophilicity and Molar Mass on the Properties of the Protein in Protein-Polymer Conjugates: The Case of PPEylated Myoglobin.

Polyphosphoesters (PPEs), a versatile class of biodegradable and biocompatible polymers, have been proposed as alternatives to poly(ethylene glycol) (PEG), which is suspected to be responsible for anaphylactic reactions in some patients after the administration of PEGylated compounds, e.g., in the current Covid-19 vaccines. We present the synthesis and characterization of a novel set of protein-polymer conjugates using the model protein myoglobin and a set of PPEs with different hydrophilicity and molar mass. We report an extensive evaluation of the (bio)physical properties of the protein within the conjugates, studying its conformation, residual activity, and thermal stability by complementary techniques (UV-vis spectroscopy, nano-differential scanning calorimetry, and fluorometry). The data underline the systematic influence of polymer hydrophilicity on protein properties. The more hydrophobic polymers destabilize the protein, the more hydrophilic PPEs protect against thermally induced aggregation and proteolytic degradation. This basic study aims at guiding the design of future PPEylated drugs and protein conjugates.

Oncolytic Nanoreactors Producing Hydrogen Peroxide for Oxidative Cancer Therapy.

In situ generation of anticancer agents at the place of the disease is a new paradigm for cancer therapy. The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to produce hydrogen peroxide. For the first time, we realized a core-shell structure with encapsulated GOX under mild synthetic conditions, which ensured high remaining activity of GOX inside of the nanoreactor. Moreover, the nanoreactor protected the loaded GOX from proteolysis and contributed to increased thermal stability of the enzyme. The nanoreactors were effectively taken up into different cancer cells, in which they produced hydrogen peroxide by consuming intracellular glucose and oxygen, thereby leading to effective death of the cancer cells. In summary, our robust nanoreactors are a promising platform for effective anticancer therapy and sustained enzyme utilization.

Enzyme-Loaded Nanoreactors Enable the Continuous Regeneration of Nicotinamide Adenine Dinucleotide in Artificial Metabolisms.

Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme for numerous biocatalytic pathways. While in nature, NAD+ is continuously regenerated from NADH by enzymes, all synthetic NAD+ regeneration strategies require a continuous supply of expensive reagents and generate byproducts, making these strategies unattractive. In contrast, we present an artificial enzyme combination that produces NAD+ from oxygen and water continuously; no additional organic substrates are required once a minimal amount pyruvate is supplied. Three enzymes, i.e., LDH, LOX, and CAT, are covalently encapsulated into a substrate-permeable silica nanoreactor by a mild fluoride-catalyzed sol-gel process. The enzymes retain their activity inside of the nanoreactors and are protected against proteolysis and heat. We successfully used NAD+ from the nanoreactors for the continuous production of NAD+ i) to sense glucose in artificial glucose metabolism, and ii) to reduce the non-oxygen binding methemoglobin to oxygen-binding hemoglobin. This latter conversion might be used for the treatment of Methemoglobinemia. We believe that this versatile tool will allow the design of artificial NAD+ -dependent metabolisms or NAD+ -mediated redox-reactions.

Membrane Engineering: Phase Separation in Polymeric Giant Vesicles.

Cell membranes exhibit elaborate lipidic patterning to carry out a myriad of functions such as signaling and trafficking. Domain formation in giant unilamellar vesicles (GUVs) is thus of interest for understanding fundamental biological processes and to provide new prospects for biocompatible soft materials. Lipid rearrangements in lipidic GUVs and lipid/polymer GUVs are extensively studied whereas polymer/polymer hybrid GUVs remain evasive. Here, the focus is on the thermodynamically driven phase separation of amphiphilic polymers in GUVs. It is demonstrated that polymer phase separation is entropically dictated by hydrophobic block incompatibilities and that films topology can help to determine the outcome of polymeric phase separation in GUVs. Lastly, Janus-GUVs are obtained and GUVs exhibit a single large domain by using a compatibilizing hydrophobic block copolymer.

Fungicide-loaded and biodegradable xylan-based nanocarriers.

The delivery of agrochemicals is typically achieved by the spraying of fossil-based polymer dispersions, which might accumulate in the soil and increase microplastic pollution. A potentially sustainable alternative is the use of biodegradable nano- or micro-formulations based on biopolymers, which can be degraded selectively by fungal enzymes to release encapsulated agrochemicals. To date, no hemicellulose nanocarriers for drug delivery in plants have been reported. Xylan is a renewable and abundant feedstock occurring naturally in high amounts in hemicellulose - a major component of the plant cell wall. Herein, xylan from corncobs was used to produce the first fungicide-loaded xylan-based nanocarriers by interfacial polyaddition in an inverse miniemulsion using toluene diisocyanate (TDI) as a crosslinking agent. The nanocarriers were redispersed in water and the aqueous dispersions were proven to be active in vitro against several pathogenic fungi, which are responsible for fungal plant diseases in horticulture or agriculture. Besides, empty xylan-based nanocarriers stimulated the growth of fungal mycelium, which indicated the degradation of xylan in the presence of the fungi, and underlined the degradation as a trigger to release a loaded agrochemical. This first example of crosslinked xylan-based nanocarriers expands the library of biodegradable and biobased nanocarriers for agrochemical release and might play a crucial role for future formulations in plant protection.

Bio-Based Lignin Nanocarriers Loaded with Fungicides as a Versatile Platform for Drug Delivery in Plants.

Lignin-based nano- and microcarriers are a promising biodegradable drug delivery platform inside of plants. Many wood-decaying fungi are capable of degrading the wood component lignin by segregated lignases. These fungi are responsible for severe financial damage in agriculture, and many of these plant diseases cannot be treated today. However, enzymatic degradation is also an attractive handle to achieve a controlled release of drugs from artificial lignin vehicles. Herein, chemically cross-linked lignin nanocarriers (NCs) were prepared by aza-Michael addition in miniemulsion, followed by solvent evaporation. The cross-linking of lignin was achieved with the bio-based amines (spermine and spermidine). Several fungicides-namely, azoxystrobin, pyraclostrobin, tebuconazole, and boscalid-were encapsulated in situ during the miniemulsion polymerization, demonstrating the versatility of the method. Lignin NCs with diameters of 200-300 nm (determined by dynamic light scattering) were obtained, with high encapsulation efficiencies (70-99%, depending on the drug solubility). Lignin NCs successfully inhibited the growth of Phaeomoniella chlamydospora and Phaeoacremonium minimum, which are lignase-producing fungi associated with the worldwide occurring fungal grapevine trunk disease Esca. In planta studies proved their efficiency for at least 4 years after a single injection into Vitis vinifera ("Portugieser") plants on a test vineyard in Germany. The lignin NCs are of high interest as biodegradable delivery vehicles to be applied by trunk injection against the devastating fungal disease Esca but might also be promising against other fungal plant diseases.

Plastics and the Environment-Current Status and Challenges in Germany and Australia.

Polymers and plastics play a very important part in the modern world and contribute to people's wellbeing and comfort. However, products made of them are contributing to land- and marine-based environmental pollution due to littering and other ways of emission, and therefore threaten ecosystems worldwide. However, waste management and responses by governments and the consumer differ strongly from country to country. The current article provides an overview of several important aspects of polymer waste and plastic pollution as well as describes selected strategies to mitigate these using examples from Germany and Australia, and therefore aims to contribute to the resolution of the ever-increasing problem of unsustainable plastic consumption, disposal, and pollution.

One-Step Ring Opening Metathesis Block-Like Copolymers and their Compositional Analysis by a Novel Retardation Technique.

Using a one-step synthetic route for block copolymers avoids the repeated addition of monomers to the polymerization mixture, which can easily lead to contamination and, therefore, to the unwanted termination of chain growth. For this purpose, monomers (M1-M5) with different steric hindrances and different propagation rates are explored. Copolymerization of M1 (propagating rapidly) with M2 (propagating slowly), M1 with M3 (propagating extremely slowly) and M4 (propagating rapidly) with M5 (propagating slowly) yielded diblock-like copolymers using Grubbs' first (G1) or third generation catalyst (G3). The monomer consumption was followed by 1 H NMR spectroscopy, which revealed vastly different reactivity ratios for M1 and M2. In the case of M1 and M3, we observed the highest difference in reactivity ratios (r1 =324 and r2 =0.003) ever reported for a copolymerization method. A triblock-like copolymer was also synthesized using G3 by first allowing the consumption of the mixture of M1 and M2 and then adding M1 again. In addition, in order to measure the fast reaction rates of the G3 catalyst with M1, we report a novel retardation technique based on an unusual reversible G3 Fischer-carbene to G3 benzylidene/alkylidene transformation.

Polymer-Based Module for NAD+ Regeneration with Visible Light.

The regeneration of enzymatic cofactors by cell-free synthetic modules is a key step towards producing a purely synthetic cell. Herein, we demonstrate the regeneration of the enzyme cofactor NAD+ by photo-oxidation of NADH under visible-light irradiation by using metal-free conjugated polymer nanoparticles. Encapsulation of the light-active nanoparticles in the lumen of polymeric vesicles produced a fully organic module able to regenerate NAD+ in an enzyme-free system. The polymer compartment conferred physical and chemical autonomy to the module, allowing the regeneration of NAD+ to occur efficiently, even in harsh chemical environments. Moreover, we show that regeneration of NAD+ by the photocatalyst nanoparticles can oxidize a model substrate, in conjunction with the enzyme glycerol dehydrogenase. To ensure the longevity of the enzyme, we immobilized it within a protective silica matrix; this yielded enzymatic silica nanoparticles with enhanced long-term performance and compatibility with the NAD+ -regeneration system.

Both Poly(ethylene glycol) and Poly(methyl ethylene phosphate) Guide Oriented Adsorption of Specific Proteins.

Developing new functional biomaterials requires the ability to simultaneously repel unwanted and guide wanted protein adsorption. Here, we systematically interrogate the factors determining the protein adsorption by comparing the behaviors of different polymeric surfaces, poly(ethylene glycol) and a poly(phosphoester), and five different natural proteins. Interestingly we observe that, at densities comparable to those used in nanocarrier functionalization, the same proteins are either adsorbed (fibrinogen, human serum albumin, and transferrin) or repelled (immunoglobulin G and lysozyme) by both polymers. However, when adsorption takes place, the specific surface dictates the amount and orientation of each protein.

Functional biodegradable polymers via ring-opening polymerization of monomers without protective groups.

Biodegradable polymers are of current interest and chemical functionality in such materials is often demanded in advanced biomedical applications. Functional groups often are not tolerated in the polymerization process of ring-opening polymerization (ROP) and therefore protective groups need to be applied. Advantageously, several orthogonally reactive functions are available, which do not demand protection during ROP. We give an insight into available, orthogonally reactive cyclic monomers and the corresponding functional synthetic and biodegradable polymers, obtained from ROP. Functionalities in the monomer are reviewed, which are tolerated by ROP without further protection and allow further post-modification of the corresponding chemically functional polymers after polymerization. Synthetic concepts to these monomers are summarized in detail, preferably using precursor molecules. Post-modification strategies for the reported functionalities are presented and selected applications highlighted.

Liposomes and polymersomes: a comparative review towards cell mimicking.

Cells are integral to all forms of life due to their compartmentalization by the plasma membrane. However, living organisms are immensely complex. Thus there is a need for simplified and controllable models of life for a deeper understanding of fundamental biological processes and man-made applications. This is where the bottom-up approach of synthetic biology comes from: a stepwise assembly of biomimetic functionalities ultimately into a protocell. A fundamental feature of such an endeavor is the generation and control of model membranes such as liposomes and polymersomes. We compare and contrast liposomes and polymersomes for a better a priori choice and design of vesicles and try to understand the advantages and shortcomings associated with using one or the other in many different aspects (properties, synthesis, self-assembly, applications) and which aspects have been studied and developed with each type and update the current development in the field.

Thermo-Responsive Polymer Brushes with Side Graft Chains: Relationship Between Molecular Architecture and Underwater Adherence.

During the last few decades, wet adhesives have been developed for applications in various fields. Nonetheless, key questions such as the most suitable polymer architecture as well as the most suitable chemical composition remain open. In this article, we investigate the underwater adhesion properties of novel responsive polymer brushes with side graft chain architecture prepared using "grafting through" approach on flat surfaces. The incorporation in the backbone of thermo-responsive poly(N-isopropylacrylamide) (PNIPAm) allowed us to obtain LCST behavior in the final layers. PNIPAm is co-polymerized with poly(methyl ethylene phosphate) (PMEP), a poloyphosphoester. The final materials are characterized studying the surface-grafted polymer as well as the polymer from the bulk solution, and pure PNIPAm brush is used as reference. PNIPAm-g-PMEP copolymers retain the responsive behavior of PNIPAm: when T > LCST, a clear switching of properties is observed. More specifically, all layers above the critical temperature show collapse of the chains, increased hydrophobicity and variation of the surface charge even if no ionizable groups are present. Secondly, effect of adhesion parameters such as debonding rate and contact time is studied. Thirdly, the reversibility of the adhesive properties is confirmed by performing adhesion cycles. Finally, the adhesive properties of the layers are studied below and above the LCST against hydrophilic and hydrophobic substrates.