Block Copolymer Self-assembly: Exploitation of Hydrogen Bonding for Nanoparticle Morphology Control via Incorporation of Triazine Based Comonomers by RAFT Polymerization.

Synthesis of polymeric nanoparticles of controlled non-spherical morphology is of profound interest for a wide variety of potential applications. Self-assembly of amphiphilic diblock copolymers is an attractive bottom-up approach to prepare such nanoparticles. In the present work, RAFT polymerization is employed to synthesize a variety of poly(N,N-dimethylacrylamide)-b-poly[butyl acrylate-stat-GCB] copolymers, where GCB represents vinyl monomer containing triazine based Janus guanine-cytosine nucleobase motifs featuring multiple hydrogen bonding arrays. Hydrogen bonding between the hydrophobic blocks exert significant influence on the morphology of the resulting nanoparticles self-assembled in water. The Janus feature of the GCB moieties makes it possible to use a single polymer type in self-assembly, unlike previous work exploiting, e.g., thymine-containing polymer and adenine-containing polymer. Moreover, the strength of the hydrogen bonding interactions enables use of a low molar fraction of GCB units, thereby rendering it possible to use the present approach for copolymers based on common vinyl monomers for the development of advanced nanomaterials.

3D Printed Solid Polymer Electrolytes with Bicontinuous Nanoscopic Domains for Ionic Liquid Conduction and Energy Storage.

Solid polymer electrolytes (SPEs) offer several advantages compared to their liquid counterparts, and much research has focused on developing SPEs with enhanced mechanical properties while maintaining high ionic conductivities. The recently developed polymerization-induced microphase separation (PIMS) technique offers a straightforward pathway to fabricate bicontinuous nanostructured materials in which the mechanical properties and conductivity can be independently tuned. In this work SPEs with tunable mechanical properties and conductivities are prepared via digital light processing 3D printing, exploiting the PIMS process to achieve nanostructured ion-conducting materials for energy storage applications. A rigid crosslinked poly(isobornyl acrylate-stat-trimethylpropane triacrylate) scaffold provided materials with room temperature shear modulus above 400 MPa, while soft poly(oligoethylene glycol methyl ether acrylate) domains containing the ionic liquid 1-butyl-3-methylimidazolium bis-(trifluoromethyl sulfonyl)imide endowed the material with ionic conductivity up to 1.2 mS cm-1 at 30 °C. These features make the 3D-printed SPE very competitive for applications in all solid energy storage devices, including supercapacitors.

3D Printing Nanostructured Solid Polymer Electrolytes with High Modulus and Conductivity.

The development of advanced solid-state energy-storage devices is contingent upon finding new ways to produce and manufacture scalable, high-modulus solid-state electrolytes that can simultaneously provide high ionic conductivity and robust mechanical integrity. In this work, an efficient one-step process to manufacture solid polymer electrolytes composed of nanoscale ion-conducting channels embedded in a rigid crosslinked polymer matrix via Digital Light Processing 3D printing is reported. A visible-light-mediated polymerization-induced microphase-separation approach is utilized, which produces materials with two chemically independent nanoscale domains with highly tunable nanoarchitectures. By producing materials containing a poly(ethylene oxide) domain swelled with an ionic liquid, robust solid polymer electrolytes with outstanding room-temperature (22 °C) shear modulus (G' > 108 Pa) and ionic conductivities up to σ = 3 × 10-4 S cm-1 are achieved. The nanostructured 3D-printed electrolytes are fabricated into a custom geometry and employed in a symmetric carbon supercapacitor, demonstrating the scalability of the fabrication and the functionality of the electrolyte. Critically, these high-performance materials are manufactured on demand using inexpensive and commercially available 3D printers, which allows the facile modular design of solid polymer electrolytes with custom geometries.

A Tunable Tumor Microenvironment through Recombinant Bacterial Collagen-Hyaluronic Acid Hydrogels.

Laboratory models of the tumor microenvironment require control of mechanical and biochemical properties to ensure accurate mimicry of patient disease. In contrast to pure natural or synthetic materials, hybrid approaches that pair recombinant protein fragments with synthetic scaffolding show many advantages. Here we demonstrate production of a recombinant bacterial collagen-like protein (CLP) for thiol-ene pairing to norbornene functionalized hyaluronic acid (NorHA). The resultant hydrogel material shows an adjustable modulus with evidence for strain-stiffening behavior that resembles natural tumor matrices. Cysteine terminated peptide binding motifs are incorporated to adjust the cell-adhesion points. The modular hybrid gel shows good biocompatibility and was demonstrated to control cell adhesion, proliferation, and the invasive properties of MCF7 and MD-MBA-231 breast adenocarcinoma cells. The ease in which multiple structural and bioactive components can be integrated provides a robust framework to form models of the tumor microenvironment for fundamental studies and drug development.

Polymeric Nanofibers of Various Degrees of Cross-Linking as Fillers in Poly(styrene-stat-n-butyl acrylate) Nanocomposites: Overcoming the Trade-Off between Tensile Strength and Stretchability.

Synthesis of light polymer nanocomposites with high strength and toughness has been a significant interest for its potential applications in industry. Herein, the authors have synthesized polymerization-induced self-assembly (PISA) derived nanodimensional polymeric worm (fiber) reinforced polymer nanocomposites by a simple and environmentally friendly synthesis process without the addition of volatile organic compounds. PISA-derived worms with a core-forming block of low glass transition temperature (Tg  ≈ 27.1 °C) comprising poly(styrene-stat-n-butyl acrylate) have been employed as reinforcing filler. The influence of core-segment cross-linking on reinforcement efficiency has been explored by comparing noncross-linked worms, and worms cross-linked with a small amount of ethylene glycol diacrylate introduced at t = 0 h or t = 2 h of polymerization. Upon addition of 1 wt% of noncross-linked, t = 0 h cross-linked, and t = 2 h cross-linked worms, toughness of polymer nanocomposites can be enhanced by 62%, 114%, and 120%, respectively. The results suggest that the reinforcement efficiency of worms is significantly influenced by the cross-linking of core-segments regardless of cross-linking methods. This work broadens the understanding in application of PISA-derived worms as reinforcing filler by demonstrating the efficient reinforcement with low Tg worms.

ROS-Mediated Anti-Angiogenic Activity of Cerium Oxide Nanoparticles in Melanoma Cells.

Angiogenesis plays a key role in cancer progression, including transition to the metastatic phase via reactive oxygen species (ROS)-dependent pathways, among others. Antivascular endothelial growth factor (VEGF) antibodies have been trialed as an anti-angiogenic therapy for cancer but are associated with high cost, limited efficacy, and side effects. Cerium oxide nanoparticles (nanoceria) are promising nanomaterials for biomedical applications due to their ability to modulate intracellular ROS. Nanoceria can be produced by a range of synthesis methods, with chemical precipitation as the most widely explored. It has been reported that chemical precipitation can fine-tune primary particle size where a limited number of synthesis parameters were varied. Here, we explore the effect of temperature, precipitating agent concentration and rate of addition, stirring rate, and surfactant concentration on nanoceria primary particle size using a fractional factorial experimental design approach. We establish a robust synthesis method for faceted nanoceria with primary particle diameters of 5-6 nm. The nanoceria are not cytotoxic to a human melanoma cell line (Mel1007) at doses up to 400 µg/mL and are dose-dependently internalized by the cells. The intracellular ROS level for some cells that internalized the nanoceria is reduced, which correlates with a dose-dependent reduction in angiogenic gene expression including VEGF. These findings contribute to our knowledge of the anti-angiogenic effects of nanoceria and help to develop our understanding of potentially new anti-angiogenic agents for combination cancer therapies.

Synthesis of Multicompositional Onion-like Nanoparticles via RAFT Emulsion Polymerization.

Synthesis of multicompositional polymeric nanoparticles of diameters 100-150 nm comprising well-defined multiblock copolymers reaching from the particle surface to the particle core was conducted using surfactant-free aqueous macroRAFT emulsion polymerization. The imposed constraints on chain mobility as well as chemical incompatibility between the blocks result in microphase separation, leading to formation of an onion-like multilayered particle morphology with individual layer thicknesses of approximately 20 nm. The approach provides considerable versatility in particle morphology design as the composition of individual layers as well as the number of layers can be tailored as desired, offering more complex particle design compared to approaches relying on self-assembly of preformed diblock copolymers within particles. Microphase separation can occur in these systems under conditions where the corresponding bulk system would not theoretically result in microphase separation.

Surface modification of nanofiltration membranes to improve the removal of organic micropollutants: Linking membrane characteristics to solute transmission.

Surface modification of nanofiltration (NF) membranes has great potential to improve the removal of organic micropollutants (OMs) by NF membranes. This study used polydopamine (PDA) as a model coating to comprehensively link the changes in membrane properties with the changes in transmission of 34 OMs. The membrane characterization demonstrated that a thicker, denser, and more hydrophilic PDA coating can be achieved by increasing the PDA deposition time from 0.5 to 4 hours. Overall, the transmissions of target OMs were reduced by PDA-coated NF membranes compared to unmodified NF membranes. The neutral hydrophobic compounds showed lower transmissions for longer PDA coating (PDA4), while the neutral hydrophilic compounds tended to show lower transmissions for shorter PDA coating (PDA0.5). To explain this, competing effects provided by the PDA coatings are proposed including sealing defects, inducing cake-enhanced concentration polarization in the coating layer for neutral hydrophilic compounds, and weakened hydrophobic adsorption for neutral hydrophobic compounds. For charged compounds, PDA4 with the greatest negative charge among the PDA-coated membranes showed the lowest transmission. Depending on the molecular size and hydrophilicity of the compounds, the transmission of OMs by the PDA4 coating could be reduced by 70% with only a 26.4% decline in water permeance. The correlations and mechanistic insights provided by this work are highly useful for designing membranes with specific surface properties via surface modification to improve the removal of OMs without compromising water production.

Digital analysis of polydiacetylene quality tags for contactless monitoring of milk.

The incorporation of colorimetric sensors as quality indicators in food packaging is an exciting new area of research that could improve food management. The standard approach, however, demands a reliable interface between the sensor and the food and risks food contamination which is a significant consumer concern. To overcome this challenge, herein, we develop a polydiacetylene/phospholipid agarose-based sensor that encapsulates milk in the hydrogel matrix during synthesis. The chemical recognition of free fatty acids, a product of microbial spoilage of the encapsulated milk, induces a gradual blue to red color change in the sensor. We demonstrate that the new composite material exhibits the same spoilage kinetics as regular liquid milk (digital colorimetric response 28 ± 1% and 27 ± 3% respectively), indicating the agarose does not preserve the milk ingredients nor inhibit the detection mechanism of the polydiacetylene sensors. As a result, this sensor can be attached to the external surface of food packaging to provide an indirect indication of food quality without the need for contact with the milk product. The quality tags we present can be "switched" on and off using dehydration and rehydration, removing the need for in situ manufacturing and allowing storage before use. We show that the quality tags produce a similar digital colorimetric response of 21 ± 2% to indicate milk spoilage after rehydration. The color change of the quality tags could not be analyzed using absorption spectroscopy, the standard technique for polydiacetylenes, due to the opacity that milk imparts on the sample. To solve this problem, we develop digital colorimetric analysis software using the Python programming language to describe the extent of color change in polydiacetylene materials and develop a new metric termed the Digital Colorimetric Response that describes polydiacetylene response with excellent linearity (R2 = 0.96). The software is programmed to employ statistical cleaning techniques that automatically remove image noise and outliers based on a pixel's grayscale Z-score. This new approach to sensor design increases practicality and could be extended to the contactless quality monitoring of other foods, medicines and other products whose safety or quality is jeopardized with direct sensor contact.

Ultra-Low Molecular Weight Photoswitchable Hydrogelators.

Two photoswitchable arylazopyrozoles form hydrogels at a concentration of 1.2 % (w/v). With a molecular weight of 258.28 g mol-1 , these are the lowest known molecular weight hydrogelators that respond reversibly to light. Photoswitching of the E- to the Z-form by exposure to 365 nm light results in a macroscopic gel→sol transition; nearly an order of magnitude reduction in the measured elastic and loss moduli. In the case of the meta-arylazopyrozole, cryogenic transmission electron microscopy suggests that the 29±7 nm wide sheets in the E-gel state narrow to 13±2 nm upon photoswitching to the predominantly Z-solution state. Photoswitching for meta-arylazopyrozole is reversible through cycles of 365 nm and 520 nm excitation with little fatigue. The release of a rhodamine B dye encapsulated in gels formed by the arylazopyrozoles is accelerated more than 20-fold upon photoswitching with 365 nm light, demonstrating these materials are suitable for light-controlled cargo release.

Porphyrinic Zirconium Metal-Organic Frameworks (MOFs) as Heterogeneous Photocatalysts for PET-RAFT Polymerization and Stereolithography.

In this study, porphyrinic zirconium (Zr) MOFs were investigated as heterogeneous photocatalysts for photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization of various monomers under a broad range of wavelengths, producing polymers with high monomer conversions, narrow molecular weight distributions, low dispersity and good chain-end fidelity. Screening of various porphyrinic Zr-MOFs (Zn) containing Zn-metalled porphyrinic ligands demonstrated that MOF-525 (Zn) with the smallest size had the best photocatalytic activity in PET-RAFT polymerization, due to enhanced dispersion and light penetration. Oxygen tolerance and temporal control were also demonstrated during MOF catalysed PET-RAFT. Results suggested that the polymerization rates were significantly affected by changing the size and surface area of MOFs, and the heterogeneous MOF photocatalysts could be easily separated and recycled for up to five independent PET-RAFT polymerizations without an obvious decrease in efficiency. Finally, the MOF photocatalysts were utilized to create three-dimensional polymeric objects with high resolution via visible light mediated stereolithography in an open-air environment.

Spatial and Temporal Control of CRISPR-Cas9-Mediated Gene Editing Delivered via a Light-Triggered Liposome System.

The CRISPR-Cas9 and related systems offer a unique genome-editing tool allowing facile and efficient introduction of heritable and locus-specific sequence modifications in the genome. Despite its molecular precision, temporal and spatial control of gene editing with the CRISPR-Cas9 system is very limited. We developed a light-sensitive liposome delivery system that offers a high degree of spatial and temporal control of gene editing with the CRISPR-Cas9 system. We demonstrated its efficient protein release by respectively assessing the targeted knockout of the eGFP gene in human HEK293/GFP cells and the TNFAIP3 gene in TNFα-induced HEK293 cells. We further validated our results at a single-cell resolution using an in vivo eGFP reporter system in zebrafish (77% knockout). These findings indicate that light-triggered liposomes may have new options for precise control of CRISPR-Cas9 release and editing.

Dual Role of Doxorubicin for Photopolymerization and Therapy.

In this study, we report dual roles for doxorubicin (DOX), which can serve as an antitumor drug as well as a cocatalyst for a photoliving radical polymerization. DOX enhances the polymerization rates of a broad range of monomers, including acrylamide, acrylate, and methacrylates, allowing for high monomer conversion and well-defined molecular weights under irradiation with a blue light-emitting diode light (λmax = 485 nm, 2.2 mW/cm2). Utilizing this property, the photopolymerization of N,N-diethylacrylamide was performed in the presence of a poly(oligo(ethylene glycol) methyl ether acrylate) macroreversible addition-fragmentation chain transfer (macroRAFT) agent to prepare polymeric nanoparticles via aqueous polymerization-induced self-assembly (PISA). By varying the monomer:macroRAFT ratio, spherical polymeric nanoparticles of various diameters could be produced. Most notably, DOX was successfully encapsulated into the hydrophobic core of nanoparticles during the PISA process. The DOX-loaded nanoparticles were effectively uptaken into tumor cells and significantly inhibited the proliferation of tumor cells, demonstrating that the DOX bioactivity was not affected by the polymerization reaction.

A Polydiacetylene-Based Colorimetric Sensor as an Active Use-By Date for Plant-Based Milk Alternatives.

Existing date marking tools, such as use-by and sell-by dates, fail to inform decision-making throughout food distribution because they do not adapt to storage conditions such as temperature. Polymer-based sensors can be incorporated into food packaging to provide an indication of food quality in real time, which can greatly reduce waste. This work identifies free fatty acid (FFA) as a marker for the quality of plant-based milk and demonstrates the first detection tool for the freshness of almond milk using phospholipid-doped polydiacetylene (PDA) vesicles. The sensor discriminates between triglycerides and FFA by a visible color change and can therefore be used to track fat metabolism during food spoilage. The interaction between FFA and PDA is investigated by electron microscopy and dynamic-light-scattering studies. PDA vesicles are then fabricated in agarose and used to discriminate between fresh and spoiled almond milk. Upon exposure of the PDA/agarose sensor to spoiled almond milk, a visible blue-to-red color change is induced in the film, which is correlated with FFA concentration in the samples. Incorporation of this technology into food packaging can be used to indicate food quality in real time, surpassing the efficacy of current date marking tools to reduce food waste.

A polydiacetylene-based colorimetric sensor as an active use-by date indicator for milk.

Current food date marking tools fail to take into account variables that impact shelf life, leading to food waste and posing human health risks. Herein, we develop a polydiacetylene/zinc oxide (PDA/ZnO) colorimetric sensor that can indicate milk freshness in real time. The PDA/ZnO system is engineered to indicate the freshness of full cream milk by monitoring its pH based on lactic acid concentration, an indicator of bacterial spoilage. The sensitivity is tuned by selection of the diacetylene monomers from which it is composed. Designs constructed from shorter chain diacetylenes are found to undergo chromatic transitions at a lower lactic acid concentration. Two new methods to tune PDA/ZnO sensitivity to lactic acid are explored, including relocation of the diacetylene functional group and lipid doping. A system constructed from 5,7-hexadecadiynoic acid (HDDA) and ZnO can discriminate between fresh (pH 6.8-6.0), spoiling (pH 6.0-4.5), and spoiled milk (pH 4.5-4.0) by a respective blue to purple to red color change. The chromatic stability of the PDA/ZnO sensor in food is studied as previous reports have shown the system to be unstable. We present a new method that stabilizes the nanocomposite by pre-exposure to the food matrix prior to photopolymerization.

Synthesis of diamine functionalised graphene oxide and its application in the fabrication of electrically conducting reduced graphene oxide/polymer nanocomposite films.

The focus of research in diamine functionalised graphene oxide (GO) has been limited to the use of diamines either as crosslinker or to achieve simultaneous functionalisation, reduction and stitching of GO sheets, especially in the case of ethylene diamine (EDA). Controlling the extent of stitching and functionalisation has to date remained a challenge. In particular, synthesis of colloidally stable monofunctionalised GO-NH2 with dangling amine groups using diamines has remained elusive. This has been the limiting factor towards the utility of EDA functionalised GO (GO-NH2) in the field of polymer-based nanocomposites. We have synthesised colloidally stable GO-NH2 with dangling amine groups and subsequently demonstrated its utility as a surfactant to synthesize colloidally stable waterborne polymer nanoparticles with innate affinity to undergo film formation at room temperature. Thermally annealed dropcast polymer/GO-NH2 nanocomposite films exhibited low surface roughness (∼1 µm) due to the homogeneous distribution of functionalised GO sheets within the polymer matrix as observed from confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy. The films exhibited considerable electrical conductivity (∼0.8 S m-1), demonstrating the potential of the GO-NH2/polymer nanocomposite for a wide range of applications.

Gradient Polymerization-Induced Self-Assembly: A One-Step Approach.

In this work, the authors report a novel single-step, one-pot process for the synthesis of self-assembled nanoparticles using a polymerization-induced self-assembly (PISA) mechanism. In contrast to conventional approaches employing a pre-formed macromolecular stabilizer, the disparate reactivities between two monomers, oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and diacetone acrylamide (DAAm), are exploited instead to synthesize a gradient copolymer directly in aqueous solution. Due to the hydrophobicity of poly(DAAm), these gradient copolymers can self-assemble in situ to form spheres and worms stabilized by the OEGMA residues. A surprisingly broad range of parameters are identified in which the worm morphology can be stabilized, which is highlighted by significant gelation of the reaction mixture in situ. This single-step gradient copolymerization approach to PISA is more efficient than conventional two-step syntheses. These results demonstrate improved reproducibility owing to the production of self-assembled nanoparticles directly in a one-pot and single-step synthesis.

Ambient-Temperature Waterborne Polymer/rGO Nanocomposite Films: Effect of rGO Distribution on Electrical Conductivity.

Electrically conductive polymer/rGO (reduced graphene oxide) films based on styrene and n-butyl acrylate are prepared by a variety of aqueous latex based routes involving ambient temperature film formation. Techniques based on miniemulsion polymerization using GO as surfactant and "physical mixing" approaches (i.e., mixing an aqueous polymer latex with an aqueous GO dispersion) are employed, followed by heat treatment of the films to convert GO to rGO. The distribution of GO sheets and the electrical conductivity depend strongly on the preparation method, with electrical conductivities in the range 9 × 10-4 to 3.4 × 102 S/m. Higher electrical conductivities are obtained using physical mixing compared to miniemulsion polymerization, which is attributed to the former providing a higher level of self-alignment of rGO into larger linear domains. The present results illustrate how the distribution of GO sheets within these hybrid materials can to some extent be controlled by judicious choice of preparation method, thereby providing an attractive means of nanoengineering for specific potential applications.

Hyaluronidase-4 is produced by mast cells and can cleave serglycin chondroitin sulfate chains into lower molecular weight forms.

Mast cells represent a heterogeneous cell population that is well-known for the production of heparin and the release of histamine upon activation. Serglycin is a proteoglycan that within mast cell α-granules is predominantly decorated with the glycosaminoglycans heparin or chondroitin sulfate (CS) and has a known role in granule homeostasis. Heparanase is a heparin-degrading enzyme, is present within the α-granules, and contributes to granule homeostasis, but an equivalent CS-degrading enzyme has not been reported previously. In this study, using several approaches, including epitope-specific antibodies, immunohistochemistry, and EM analyses, we demonstrate that human HMC-1 mast cells produce the CS-degrading enzymes hyaluronidase-1 (HYAL1) and HYAL4. We observed that treating the two model CS proteoglycans aggrecan and serglycin with HYAL1 and HYAL4 in vitro cleaves the CS chains into lower molecular weight forms with nonreducing end oligosaccharide structures similar to CS stub neoepitopes generated after digestion with the bacterial lyase chondroitinase ABC. We found that these structures are associated with both the CS linkage region and with structures more distal toward the nonreducing end of the CS chain. Furthermore, we noted that HYAL4 cleaves CS chains into lower molecular weight forms that range in length from tetra- to dodecasaccharides. These results provide first evidence that mast cells produce HYAL4 and that this enzyme may play a specific role in maintaining α-granule homeostasis in these cells by cleaving CS glycosaminoglycan chains attached to serglycin.