Stiffness-Dependent Intracellular Location of Cylindrical Polymer Brushes.

Cylindrical polymer brushes (CPBs) are macromolecules with nanoparticle proportions. Their modular synthesis enables tailoring of their chemical composition as well as the dialing-up of overall dimensions and physicochemical properties. In this study, two rod-like poly[(ethylene glycol) methyl ether methacrylate] (PEGMA)-based CPBs with varying stiffness but otherwise comparable features and functionality, are synthesized. Differences in particle stiffness are assessed using small angle neutron scattering (SANS). It is observed that the fate of the two CPBs within cells is distinctly different. Stiffer CPBs seem to gravitate toward the mitochondria, whereas CPBs with reduced stiffness are present in different intracellular vesicles.

Synthesis and Characterization of Bone Binding Antibiotic-1 (BBA-1), a Novel Antimicrobial for Orthopedic Applications.

Osteomyelitis and orthopedic infections are major clinical problems, limited by a lack of antibiotics specialized for such applications. In this paper, we describe the design and synthesis of a novel bone-binding antibiotic (BBA-1) and its subsequent structural and functional characterization. The synthesis of BBA-1 was the result of a two-step chemical conjugation of cationic selective antimicrobial-90 (CSA-90) and the bisphosphonate alendronate (ALN) via a heterobifunctional linker. This was analytically confirmed by HPLC, FT-IR, MS and NMR spectroscopy. BBA-1 showed rapid binding and high affinity to bone mineral in an in vitro hydroxyapatite binding assay. Kirby-Baur assays confirmed that BBA-1 shows a potent antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus comparable to CSA-90. Differentiation of cultured osteoblasts in media supplemented with BBA-1 led to increased alkaline phosphatase expression, which is consistent with the pro-osteogenic activity of CSA-90. Bisphosphonates, such as ALN, are inhibitors of protein prenylation, however, the amine conjugation of ALN to CSA-90 disrupted this activity in an in vitro protein prenylation assay. Overall, these findings support the antimicrobial, bone-binding, and pro-osteogenic activities of BBA-1. The compound and related agents have the potential to ensure lasting activity against osteomyelitis after systemic delivery.

Cylindrical Zwitterionic Particles via Interpolyelectrolyte Complexation on Molecular Polymer Brushes.

The fabrication of macromolecular architectures with high aspect ratio and well-defined internal and external morphologies remains a challenge. The combination of template chemistry and self-assembly concepts to construct peculiar polymer architectures via a bottom-up approach is an emerging approach. In this study, a cylindrical template-namely a core-shell molecular polymer brush-and linear diblock copolymers (DBCP) associate to produce high aspect ratio polymer particles via interpolyelectrolyte complexation. Induced, morphological changes are studied using cryogenic transmission electron and atomic force microscopy, while the complexation is further followed by isothermal titration calorimetry and ξ-potential measurements. Depending on the nature of the complexing DBCP, distinct morphological differences can be achieved. While polymers with a non-ionic block lead to internal compartmentalization, polymers featuring zwitterionic domains lead to a wrapping of the brush template.

Bisphosphonate-functionalized micelles for targeted delivery of curcumin to metastatic bone cancer.

Metastatic (secondary) bone cancer is one of the major causes of death in patients with advanced cancer. A lack of options for the targeted delivery of a desired therapeutic payload to multiple tumour modules located in the bone is still one of the foremost hurdles in the treatment/prevention of metastatic bone cancer. Curcumin has a proven anticancer potential with known challenges for application as a pharmaceutical agent. We have previously shown that micellar formulations could overcome some of these challenges and enhances its anti-cancer activity. In this study, we have developed a targeted drug delivery system using bisphosphonate (alendronate) conjugated Pluronic F127 micelles that could efficiently target, and specifically deliver curcumin to the osteolytic tumour microenvironment in the bone. Characterization of the formulation of curcumin-encapsulated alendronate-conjugated micelles demonstrated that the micelles have nanoscale size (∼27 nm) with a positive surface charge (+2.87 mV) and 4% drug loading. The alendronate-conjugated micelles showed significant bone-targeting potential. Rapid binding of the micelles to hydroxyapatite surface suggested that these nanoparticles are promising carriers for effective and targeted delivery of curcumin to osteolytic tumours in the bone.

Polymer Nanowires with Highly Precise Internal Morphology and Topography.

The construction of precise soft matter nanostructures in solution presents a challenge. A key focus remains on the rational design of functionalities to achieve the high morphological complexity typically found in biological systems. Advances in controlled polymerizations and self-assembly increasingly allow approaches toward complex hierarchical nanomaterials. By combining tailor-made cylindrical polymer brushes, block copolymers and interpolyelectrolyte complexation-driven self-assembly, we demonstrate a facile construction of uniformly compartmentalized and topographically structured polymeric nanowires in aqueous media. The approach offers a modular avenue in programming the internal morphology of polymer nanowires by varying the block copolymer composition and topology.

Self-Assembly of Diblock Molecular Polymer Brushes in the Spherical Confinement of Nanoemulsion Droplets.

Understanding the self-assembly behavior of polymers of various topologies is key to a reliable design of functional polymer materials. Self-assembly under confinement conditions emerges as a versatile avenue to design polymer particles with complex internal morphologies while simultaneously facilitating scale-up. However, only linear block copolymers have been studied to date, despite the increasing control over macromolecule composition and architecture available. This study extends the investigation of polymer self-assembly in confinement from regular diblock copolymers to diblock molecular polymer brushes (MPBs). Block-type MPBs with polystyrene (PS) and polylactide (PLA) compartments of different sizes are incorporated into surfactant-stabilized oil-in-water (chloroform/water) emulsions. The increasing confinement in the nanoemulsion droplets during solvent evaporation directs the MPBs to form solid nano/microparticles. Microscopy studies reveal an intricate internal particle structure, including interpenetrating networks and axially stacked lamellae of PS and PLA, depending on the PS/PLA ratio of the brushes.

Synthesis and Applications of Compartmentalised Molecular Polymer Brushes.

Polymer science is rapidly advancing towards the precise construction of synthetic macromolecules of formidable complexity. Beyond the impressive advances in control over polymer composition and uniformity enabled by the living polymerisation revolution, the introduction of compartmentalisation within polymer architectures can elevate their functionality beyond that of their constituent parts, thus offering immense potential for the production of tailor-made nanomaterials. In this Minireview, we discuss synthetic routes to complex molecular brushes with discrete chemical compartments and highlight their potential in the development of advanced materials with applications in nanofabrication, optics and functional materials.

Self-initiation of UV photopolymerization reactions using tetrahalogenated bisphenol A (meth)acrylates.

The potential of tetrachlorinated and tetrabrominated bisphenol A diacrylates and dimethacrylates for self-initiation of a radical photopolymerization was investigated. The kinetics of the photopolymerization of an acrylic model varnish containing halogenated monomers was studied by real-time FTIR spectroscopy, whereas the formation of reactive species and secondary products was elucidated by laser flash photolysis and product analysis by GC-MS after steady-state photolysis. The interpretation of the experimental data and the analysis of possible reaction pathways were assisted by quantum chemical calculations. It was shown that all halogenated monomers lead to a significant acceleration of the photopolymerization kinetics at a minimum concentration of 5 wt%. Steady-state and laser flash photolysis measurements as well as quantum chemical calculations showed that brominated and chlorinated samples do not follow the same pathway to generate radical species. Whereas chlorinated (meth)acrylates may cleave only at the C-O bonds of the carboxyl groups resulting in acrolein and oxyl radicals for initiation, brominated monomers may cleave either at the C-O bonds or at the C-Br bonds delivering aryl and bromine radicals. The quantum yields for the photolysis of the halogenated monomers were found to be in the order of 0.1 for acrylates and 0.2 for methacrylates (with an estimated error of 25%), independently of the attached Br and Cl halogens. Finally, the trihalogenated bisphenol A di(meth)acrylate radicals and the acrolein radicals were found to show the highest efficiencies for the reaction with another acrylic double bond leading to the formation of a polymer network.

Effect of Polyelectrolyte Charge Density on the Linear Viscoelastic Behavior and Processing of Complex Coacervate Adhesives.

It is well-known that the phase behavior and physicochemical and adhesive properties of complex coacervates are readily tuneable with the salt concentration of the medium. For toxicity reasons, however, the maximum applicable salt concentration in biomedical applications is typically low. Consequently, other strategies must be implemented in order to optimize the properties of the resulting complex coacervates. In this work, the effect of the charge density of a strong polyanion on the properties of complex coacervates was studied. To control this charge density, statistical anionic/charge-neutral hydrophilic copolymers were synthesized by means of an elegant protection/deprotection strategy and subsequently complexed with a strong polycation. The resulting complexes were observed to have an increasing water content as well as faster relaxation dynamics, with either increasing salt concentration or decreasing charge density. Time-salt and time-salt-charge density superpositions could be performed and showed that the relaxation mechanism of the complex coacervates remained unchanged. When the charge density was decreased, lower salt concentration complexes became suitable for viscoelastic adhesion with improved injectability. Such complex coacervates are promising candidates for injectable biomedical adhesives.

Ring-opening polymerization of emulsion-templated deep eutectic system monomer for macroporous polyesters with controlled degradability.

Biodegradable polyesters with interconnected macroporosity, such as poly(l-lactide) (PLLA) and poly(ε-caprolactone) (PCL), have gained significant importance in the fields of tissue engineering and separation. This study introduces functional macroinitiators, specifically polycaprolactone triol (PCLT) and polyethylene glycol (PEG), both OH-terminated, in the solventless ring-opening polymerization (ROP) of a liquid deep eutectic system monomer (DESm) composed of LLA and CL at a 30 : 70 molar ratio, respectively. The macroinitiators selectively initiate the organocatalyzed ROP of LLA in the DESm during the first polymerization stage, thereby modifying the PLLA architecture. This results in the formation of either branched or linear PLLA copolymers depending on the macroinitiator, PCLT and PEG, respectively. In the second stage, the ROP of the CL, which is a counterpart of the DESm, produces PCL that blends with the previously formed PLLA. The insights gained into the PLLA architectures during the first stage of the DESm ROP, along with the overall molecular weight and hydrophobicity of the resulting PLLA/PCL blend in bulk, were advantageously used to design polymerizable high internal phase emulsions (HIPEs) oil-in-DESm. By incorporating a liquid mixture of DESm and macroinitiators (PCLT or PEG), stable HIPE formulations were achieved. These emulsions sustained the efficient organocatalyzed ROP of the continuous phase at 37 °C with high conversions. The resulting polymer replicas of the HIPEs, characterized by macroporous and interconnected structures, were subjected to a degradation assay in PBS at pH 7.4 and 37 °C and remained mechanically stable for at least 30 days. Notably, they exhibited the capability to sorb crude oil in a proof-of-concept test, with a rate of 2 g g-1. The macroporous and interconnected features of the polyHIPEs, combined with their inherent degradation properties, position them as promising degradable polymeric sorbents for efficient separation of hydrophobic fluids from water.

Lipoic acid-based vitrimer-like elastomer.

Dynamic covalent networks (DCNs) are materials that feature reversible bond formation and breaking, allowing for self-healing and recyclability. To speed up the bond exchange, significant amounts of catalyst are used, which creates safety concerns. To tackle this issue, we report the synthesis of a lipoic acid-based vitrimer-like elastomer (LAVE) by combining (i) ring-opening polymerization (ROP) of lactones, (ii) lipoic acid modification of polylactones, and (iii) UV crosslinking. The melting temperature (Tm) of LAVE is below room temperature, which ensures the elastic properties of LAVE at service temperature. By carefully altering the network, it is possible to tune the Tm, as well as the mechanical strength and stretchability of the material. An increase in polylactone chain length in LAVE was found to increase strain at break from 25% to 180% and stress at break from 0.34 to 1.41 MPa. The material showed excellent network stability under cyclic strain loading, with no apparent hysteresis. The introduction of disulfide bonds allows the material to self-heal under UV exposure, extending its shelf life. Overall, this work presents an environmentally friendly approach for producing a sustainable elastomer that has potential for use in applications such as intelligent robots, smart wearable technology, and human-machine interfaces.

One-Pot Synthesis of Strong Anionic/Charge-Neutral Amphiphilic Block Copolymers.

Despite the ever more versatile polymerization techniques that are becoming available, the synthesis of macromolecules with tailored functionalities can remain a lengthy endeavor. This becomes more conspicuous when the implementation of incompatible chemistries (i.e., strong polyelectrolytes) within sequence-controlled polymers is desired, often requiring (i) polymerization, (ii) chain extension, and (iii) postpolymerization modification. Herein, we explore the production of strong anionic/charge-neutral block copolymers (BCPs) in a one-pot fashion. This straightforward three-step process includes the synthesis of a macroinitiator and chain extension via rapid and efficient photomediated atom transfer radical polymerization, followed by in situ deprotection to expose the polyanionic domains. The resulting BCPs, which are strong amphiphiles by nature, are capable of self-assembly in aqueous media, as evidenced by dynamic light scattering, small-angle X-ray scattering, ζ-potential measurements, and transmission electron microscopy. We further demonstrate the versatility of our methodology by producing several BCPs through sampling of a single reaction mixture, enabling the straightforward production of strong polymer amphiphiles.

Toward Effective and Adsorption-Based Antifouling Zipper Brushes: Effect of pH, Salt, and Polymer Design.

The undesired spontaneous deposition and accumulation of matter on surfaces, better known as fouling, is a problematic and often inevitable process plaguing a variety of industries. This detrimental process can be reduced or even prevented by coating surfaces with a dense layer of end-grafted polymer: a polymer brush. Producing such polymer brushes via adsorption presents a very attractive technique, as large surfaces can be coated in a quick and simple manner. Recently, we introduced a simple and scalable two-step adsorption strategy to fabricate block copolymer-based antifouling coatings on hydrophobic surfaces. This two-step approach involved the initial adsorption of hydrophobic-charged diblock copolymer micelles acting as a primer, followed by the complexation of oppositely charged-antifouling diblock copolymers to form the antifouling brush coating. Here, we significantly improve this adsorption-based zipper brush via systematic tuning of various parameters, including pH, salt concentration, and polymer design. This study reveals several key outcomes. First of all, increasing the hydrophobic/hydrophilic block ratio of the anchoring polymeric micelles (i.e., decreasing the hydrophilic corona) promotes adsorption to the surface, resulting in the most densely packed, uniform, and hydrophilic primer layers. Second, around a neutral pH and at a low salt concentration (1 mM), complexation of the weak polyelectrolyte (PE) blocks results in brushes with the best antifouling efficacy. Moreover, by tuning the ratio between these PE blocks, the brush density can be increased, which is also directly correlated to the antifouling performance. Finally, switching to different antifouling blocks can increase the internal density or strengthen the bound hydration layer of the brush, leading to an additional enhancement of the antifouling properties (>99% lysozyme, 87% bovine serum albumin).

Scalable and Degradable Dextrin-Based Elastomers for Wearable Touch Sensing.

Elastomer-based wearables can improve people's lives; however, frictional wear caused by manipulation may pose significant concerns regarding their durability and sustainability. To address the aforementioned issue, a new class of advanced scalable supersoft elastic transparent material (ASSETm) is reported, which offers a unique combination of scalability (20 g scale), stretchability (up to 235%), and enzymatic degradability (up to 65% in 30 days). The key feature of our design is to render native dextrin hydrophobic, which turns it into a macroinitiator for bulk ring-opening polymerization. Based on ASSETm, a self-powered touch sensor (ASSETm-TS) for touch sensing and non-contact approaching detection, possessing excellent electrical potential (up to 65 V) and rapid response time (60 ms), is fabricated. This work is a step toward developing sustainable soft electronic systems, and ASSETm's tunability enables further improvement of electrical outputs, enhancing human-interactive applications.

Scalable Fabrication of Reversible Antifouling Block Copolymer Coatings via Adsorption Strategies.

Fouling remains a widespread challenge as its nonspecific and uncontrollable character limits the performance of materials and devices in numerous applications. Although many promising antifouling coatings have been developed to reduce or even prevent this undesirable adhesion process, most of them suffer from serious limitations, specifically in scalability. Whereas scalability can be particularly problematic for covalently bound antifouling polymer coatings, replacement by physisorbed systems remains complicated as it often results in less effective, low-density films. In this work, we introduce a two-step adsorption strategy to fabricate high-density block copolymer-based antifouling coatings on hydrophobic surfaces, which exhibit superior properties compared to one-step adsorbed coatings. The obtained hybrid coating manages to effectively suppress the attachment of both lysozyme and bovine serum albumin, which can be explained by its dense and homogeneous surface structure as well as the desired polymer conformation. In addition, the intrinsic reversibility of the adhered complex coacervate core micelles allows for the successful triggered release and regeneration of the hybrid coating, resulting in full recovery of its antifouling properties. The simplicity and reversibility make this a unique and promising antifouling strategy for large-scale underwater applications.

Strong Anionic/Charge-Neutral Block Copolymers from Cu(0)-Mediated Reversible Deactivation Radical Polymerization.

Despite recent developments in controlled polymerization techniques, the straightforward synthesis of block copolymers that feature both strong anionic and charge-neutral segments remains a difficult endeavor. In particular, solubility issues may arise during the direct synthesis of strong amphiphiles and typical postpolymerization deprotection often requires harsh conditions. To overcome these challenges, we employed Cu(0)-mediated reversible deactivation radical polymerization (Cu(0)-RDRP) on a hydrophobic isobutoxy-protected 3-sulfopropyl acrylate. Cu(0)-RDRP enables the rapid synthesis of the polymer, reaching high conversions and low dispersities while using a single solvent system and low amounts of copper species. These macromolecules are straightforward to characterize and can subsequently be deprotected in a mild yet highly efficient fashion to expose their strongly charged nature. Furthermore, a protected sulfonate segment could be grown from a variety of charge-neutral macroinitiators to produce, after the use of the same deprotection chemistry, a library of amphiphilic, double-hydrophilic as well as thermoresponsive block copolymers (BCPs). The ability of these various BCPs to self-assemble in aqueous media was further studied by dynamic light scattering, ζ-potential measurements as well as atomic force and electron microscopy.

Transparent Low Molecular Weight Poly(Ethylene Glycol) Diacrylate-Based Hydrogels as Film Media for Photoswitchable Drugs.

Hydrogels have shown a great potential as materials for drug delivery systems thanks to their usually excellent bio-compatibility and their ability to trap water-soluble organic molecules in a porous network. In this study, poly(ethylene glycol)-based hydrogels containing a model dye were synthesized by ultraviolet (UV-A) photopolymerization of low-molecular weight macro-monomers and the material properties (dye release ability, transparency, morphology, and polymerization kinetics) were studied. Real-time infrared measurements revealed that the photopolymerization of the materials was strongly limited when the dye was added to the uncured formulation. Consequently, the procedure was adapted to allow for the formation of sufficiently cured gels that are able to capture and later on to release dye molecules in phosphate-buffered saline solution within a few hours. Due to the transparency of the materials in the 400⁻800 nm range, the hydrogels are suitable for the loading and excitation of photoactive molecules. These can be uptaken by and released from the polymer matrix. Therefore, such materials may find applications as cheap and tailored materials in photodynamic therapy (i.e., light-induced treatment of skin infections by bacteria, fungi, and viruses using photoactive drugs).