Self-Assembly of Rod-Coil Bottlebrush Copolymers into Degradable Nanodiscs with a UV-Triggered Self-Immolation Process.

Polymer nanodiscs, especially with stimuli-responsive features, represent an unexplored frontier in the nanomaterial landscape. Such 2D nanomaterials are considered highly promising for advanced biomedicine applications. Herein, we designed a rod-coil copolymer architecture based on an amphiphilic, tadpole-like bottlebrush copolymer, which can directly self-assemble into core-shell nanodiscs in an aqueous environment. As the bottlebrush side chains are made of amorphous, UV-responsive poly(ethyl glyoxylate) (PEtG) chains, they can undergo rapid end-to-end self-immolation upon light irradiation. This triggered nanodisc disassembly can be used to boost small molecule release from the nanodisc core, which is further aided by a morphological change from discs to spheres.

Carborane-Containing Polymers: Synthesis, Properties, and Applications.

Carboranes are an important class of electron-delocalized icosahedral carbon-boron clusters with unique physical and chemical properties, which can offer various functions to polymers including enhanced heat-resistance, tuned electronic properties and hydrophobicity, special ability of dihydrogen bond formation, and thermal neutron capture. Carborane-containing polymers have been synthesized mainly by means of step-growth polymerizations of disubstituted carborane monomers, with chain-growth polymerizations of monosubstituted carborane monomers including ATRP, RAFT, and ROMP only utilized recently. Carborane-containing polymers may find application as harsh-environment resistant materials, ceramic precursors, fluorescent materials with tuned emissive properties, novel optoelectronic devices, potential BNCT agents, and drug carriers with low cytotoxicity. This review highlights carborane-containing polymer synthesis strategies and potential applications, showcasing the versatile properties and possibilities that this unique family of boron compounds can provide to the polymeric systems.

Nanoscale polymer discs, toroids and platelets: a survey of their syntheses and potential applications.

Polymer self-assembly has become a reliable and versatile workhorse to produce polymeric nanomaterials. With appropriate polymer design and monomer selection, polymers can assemble into shapes and morphologies beyond well-studied spherical and cylindrical micellar structures. Steadfast access to anisotropic polymer nanoparticles has meant that the fabrication and application of 2D soft matter has received increasing attention in recent years. In this review, we focus on nanoscale polymer discs, toroids, and platelets: three morphologies that are often interrelated and made from similar starting materials or common intermediates. For each morphology, we illustrate design rules, and group and discuss commonly used self-assembly strategies. We further highlight polymer compositions, fundamental principles and self-assembly conditions that enable precision in bottom-up fabrication strategies. Finally, we summarise potential applications of such nanomaterials, especially in the context of biomedical research and template chemistry and elaborate on future endeavours in this space.

Water-Soluble Squaramide-Functionalized Copolymers for Anion Recognition.

A series of ethylene glycol-based squaramide-containing copolymers are synthesized via a post-polymerization functionalization strategy. Conversion of polymeric amines to squaramides is found to proceed in good yields, representing a versatile method of incorporating squaramides into polymers for anion recognition. Analysis of the polymers by UV-Vis and fluorescence spectroscopy revealed that anion binding takes place similarly to that of small-molecule squaramides. The presence of a fluorescent sensing group on polymer-bound squaramides allowed for a fluorescent sensing mechanism for anions that followed a similar trend in selectivity in aqueous DMSO solution, with selectivity observed for H2 PO4 - , AcO- and SO4 2- over other common anions tested. The anion response and selectivity towards anions is similar to that of analogous small-molecule squaramides, however polymeric squaramides exhibited a greater resistance to deprotonation by more basic anions, which is attributed to the closer proximity of individual squaramides on a macromolecule. The squaramide-containing polymers exhibited good water solubility, overcoming a common problem for anion sensors which are typically not sufficiently soluble in water to function in many required applications. Despite no anion binding being observed in water, this study represents a simple and effective method of creating fully water-soluble anion receptors which may be adapted to give improved binding affinity and selectivity depending on the anion binding moiety.

Synthesis and Evaluation of Functionalized Polyurethanes for pH-Responsive Delivery of Compounds in Chronic Wounds.

Chronic wounds, depending on the bacteria that caused the infection, can be associated with an extreme acidic or basic pH. Therefore, the application of pH-responsive hydrogels has been instigated for the delivery of therapeutics to chronic wounds. Herein, with the aim of developing a flexible pH-responsive hydrogel, we functionalized hydrophilic polyurethanes with either cationic (polyethylene imine) or anionic (succinic anhydride) moieties. A comprehensive physicochemical characterization of corresponding polymers was carried out. Particularly, when tested in aqueous buffers, the surface charge of hydrogel films was closely correlated with the pH of the buffers. The loading of the cationic and anionic hydrogel films with various compound models (bromophenol blue; negatively charged or Pyronin Y; positively charged) showed that the electrostatic forces between the polymeric backbone and the compound model will determine the ultimate release rate at any given pH. The potential application of these films for chronic wound drug delivery was assessed by loading them with an antibiotic (ciprofloxacin). In vitro bacterial culturing was performed using Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Results showed that at the same drug dosage, different release profiles achievable from cationic and anionic polyurethanes can yield different degrees of an antibacterial effect. Overall, our results suggest the potential application of cationic and anionic hydrophilic polyurethanes as flexible pH-responsive materials for the delivery of therapeutics to chronic wounds.

Tunable Polymer Nanoreactors from RAFT Polymerization-Induced Self-Assembly: Fabrication of Nanostructured Carbon-Coated Anatase as Battery Anode Materials with Variable Morphology and Porosity.

We demonstrate a modular synthesis approach to yield mesoporous carbon-coated anatase (denoted as TiO2/C) nanostructures. Combining polymerization-induced self-assembly (PISA) and reversible addition-fragmentation chain-transfer (RAFT) dispersion polymerization enabled the fabrication of uniform core-shell polymeric nanoreactors with tunable morphologies. The nanoreactors comprised of a poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) shell and a poly(benzyl methacrylate) (PBzMA) core. We selected worm-like and vesicular morphologies to guide the nanostructuring of a TiO2 precursor, namely, titanium(IV) bis(ammonium lactato)dihydroxide (TALH). Subsequent carbonization yielded nanocrystalline anatase and simultaneously introduced a porous carbon framework, which also suppressed the crystal growth (∼5 nm crystallites). The as-prepared TiO2/C materials comprised of a porous structure, with large specific surface areas (>85 m2/g) and various carbon contents (20-30 wt %). As anode components in lithium-ion batteries, our TiO2/C nanomaterials improved the cycling stability, facilitated high overall capacities, and minimized the capacity loss compared to both their sans carbon and commercial anatase analogues.

Molecular polymer bottlebrushes in nanomedicine: therapeutic and diagnostic applications.

Molecular polymer bottlebrushes are densely grafted, individual macromolecules with nanoscale proportions. The last decade has seen an increased focus on this material class, especially in nanomedicine and for biomedical applications. This Feature Article provides an overview of major developments in this area to highlight the many opportunities that these polymer architectures bring to nano-bio research. The article covers aspects of bottlebrush synthesis and summarises their use in drug and gene delivery, imaging, as theranostics and as prototype materials to correlate nanoparticle structure and composition to biological function and behaviour. Areas for future research in this area are discussed.

Tuning the Hydrophilic-Hydrophobic Balance of Molecular Polymer Bottlebrushes Enhances their Tumor Homing Properties.

Nanoparticle (NP)-based drug delivery systems are promising in anticancer therapy, capable of delivering cargo with superior selectivity and achieving enhanced tumor accumulation compared to small-molecule therapeutics. As more efforts are being devoted to NP development, molecular polymer bottlebrushes (MPBs) have gained attention as a potential drug delivery vehicle. To date, the influence of various MPB parameters such as size, shape, and surface charge in determining tumor penetrability have been systematically probed. However, the role of amphiphilicity, specifically the hydrophilic-hydrophobic balance, remains unexplored. In this study, a series of MPBs are employed with varied hydrophobicity levels to reveal a dependence between MPB composition, cell association, and tumor homing. The data indicates that increasing levels of hydrophobicity in MPBs (to a certain level) demonstrate only marginal effects in vitro but reveals enhanced tumor homing in a mouse model of ovarian cancer in vivo, where more hydrophilic MPBs exhibit low tissue deposition and low tumor homing. In contrast, more hydrophobic MPBs show significant tumor accumulation and homing due to their engineered hydrophobicity.

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.

A Regenerable Biosensing Platform for Bacterial Toxins.

Waterborne diarrheal diseases such as travelers' diarrhea and cholera remain a threat to public health in many countries. Rapid diagnosis of an infectious disease is critical in preventing the escalation of a disease outbreak into an epidemic. Many of the diagnostic tools for infectious diseases employed today are time-consuming and require specialized laboratory settings and trained personnel. There is hence a pressing need for fit-for-purpose point-of-care diagnostic tools with emphasis in sensitivity, specificity, portability, and low cost. We report work toward thermally reversible biosensors for detection of the carbohydrate-binding domain of the Escherichia coli heat-labile enterotoxin (LTB), a toxin produced by enterotoxigenic E. coli strains, which causes travelers' diarrhea. The biosensing platform is a hybrid of two materials, combining the optical properties of porous silicon (pSi) interferometric transducers and a thermoresponsive multivalent glycopolymer, to enable recognition of LTB. Analytical performance of our biosensors allows us to detect, using a label-free format, sub-micromolar concentrations of LTB in solution as low as 0.135 µM. Furthermore, our platform shows a temperature-mediated "catch-and-release" behavior, an exciting feature with potential for selective protein capture, multiple readouts, and regeneration of the sensor over consecutive cycles of use.

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.

Circular Intensity Differential Scattering Reveals the Internal Structure of Polymer Fibrils.

The optical and electronic properties of π-conjugated polymers in organic electronic devices depend on their intra- and interchain interactions, dictated by the internal arrangement of the polymer chains in an amorphous or semicrystalline aggregated state. Here, we discuss the utility of circular intensity differential scattering (CIDS) of circularly polarized light as a sensitive probe to identify the internal arrangement of the polymer chains in helical polymer aggregates. We advance existing theoretical models to utilize the CIDS response and extract structural properties such as the size, orientation, and periodicity of a polymer aggregate. As an example, we analyze the CIDS signatures of helically assembled fibrillar aggregates of a chiral polymer poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzothiadiazole)] (PFBT) in solution and reveal that PFBT fibrils incorporate at least five intertwined polymer chains. We anticipate our approach can be extended more generally to investigate the internal arrangement of supramolecular assemblies of a wide range of fibrillar aggregates of π-conjugated polymers.

Confinement Assembly of ABC Triblock Terpolymers for the High-Yield Synthesis of Janus Nanorings.

Block copolymers are versatile building blocks for the self-assembly of functional nanostructures in bulk and solution. While spheres, cylinders, and bilayer sheets are thermodynamically preferred shapes and frequently observed, ring-shaped nanoparticles are more challenging to realize due to energetic penalties that originate from their anisotropic curvature. Today, a handful of concepts exist that produce core-shell nanorings, while more complex ( e. g., patchy) nanorings are currently out of reach and have only been predicted theoretically. Here, we demonstrate that confinement assembly of properly designed ABC triblock terpolymers is a general route to synthesize Janus nanorings in high purity. The triblock terpolymer self-assembles in the spherical confinement of nanoemulsion droplets into prolate ellipsoidal microparticles with an axially stacked lamellar-ring ( lr)-morphology. We clarified and visualized this complex, yet well-ordered, morphology with transmission electron tomography. Blocks A and C formed stacks of lamellae with the B microdomain sandwiched in-between as nanorings. Cross-linking of the B-rings allowed disassembly of the microparticles into Janus nanorings carrying two strictly separated polymer brushes of A and C on the top and bottom. Decreasing the B volume leads to Janus spheres and rods, while an increase of B results in perforated and filled Janus disks. The confinement assembly of ABC triblock terpolymers is a general process that can be extended to other block chemistries and will allow to synthesize a large variety of complex micro- and nanoparticles that inspire studies in self-assembly, interfacial stabilization, colloidal packing, and nanomedicine.

Engineering Protective Polymer Coatings for Liver Microtissues.

Three-dimensional (3D) hepatocyte microtissues (MT), also known as spheroids, have proven to be advantageous in providing more accurate information and physiologically relevant and predictive data for liver-related in vivo tests; therefore, spheroids have increasingly been used to study hepatotoxicity, drug delivery to the liver, and tissue engineering. However, variabilities in the generation of 3D MT remain a major challenge. Methods that encapsulate and protect hepatocytes offer a promising pathway in prolonging cell survival, as well as maintaining its liver cell functions. Herein, we studied the encapsulation and resultant protective effects of hydrogen bonded, biocompatible polymer coatings for hepatocyte MT in 3D cell culture. We exposed the MT to hepatotoxic nanomaterials (NMs), such as graphene oxide (GO) and cobalt oxide (Co3O4), to assess the protective effects of poly(vinylpyrrolidone) (PVPON) and tannic acid (TA) coatings. The polymer coating allowed the MT to maintain its morphology. More significantly, it increased the viability of hepatocyte-composed MT by hampering the cellular interaction between hostile NMs and hepatocytes. Based on alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, the liver cell function was maintained throughout the coating process, including after NM treatment. The study provides a straightforward and safe methodology for maintaining the morphology as well as cellular function of hepatocyte MT in vitro.

Visible-Light-Driven MADIX Polymerisation via a Reusable, Low-Cost, and Non-Toxic Bismuth Oxide Photocatalyst.

The continuous amalgamation of photocatalysis into existing reversible deactivation radical polymerisation (RDRP) processes has initiated a rapidly propagating area of polymer research in recent years. We introduce bismuth oxide (Bi2 O3 ) as a heterogeneous photocatalyst for polymerisations, operating at room temperature with visible light. We demonstrate formidable control over degenerative chain-transfer polymerisations, such as macromolecular design by interchange of xanthate (MADIX) and reversible addition-fragmentation chain-transfer (RAFT) polymerisation. We achieved narrow molecular weight distributions and attribute the excellent temporal control of a photo-induced electron transfer (PET) process. This methodology was employed to synthesise diblock copolymers combining differently activated monomers. The Bi2 O3 catalyst system has the additional benefits of low toxicity, reusability, low-cost, and ease of removal from the reaction mixture.

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.