Rapid production of block copolymer nano-objects via continuous-flow ultrafast RAFT dispersion polymerisation

Ultrafast RAFT polymerisation is exploited under dispersion polymerisation conditions for the synthesis of poly(dimethylacrylamide)-b-poly(diacetoneacrylamide) (PDMAmx-b-PDAAmy) diblock copolymer nanoparticles. This process is conducted within continuous-flow reactors, which are well suited to fast reactions and can easily dissipate exotherms making the process potentially scalable. Transient kinetic profiles obtained in-line via low-field flow nuclear magnetic resonance spectroscopy (flow-NMR) confirmed the rapid rate of polymerisation whilst still maintaining pseudo first order kinetics. Gel permeation chromatography (GPC) reported molar mass dispersities, Đ < 1.3 for a series of PDMAmx-b-PDAAmy diblock copolymers (x = 46, or 113; y = 50, 75, 100, 150 and 200) confirming control over molecular weight was maintained. Particle characterisation by dynamic light scattering (DLS) and transmission electron microscopy (TEM) indicated successful preparation of spheres and a majority worm phase at 90 °C but the formation of vesicular morphologies was only possible at 70 °C. To maintain the rapid rate of reaction at this lower temperature, initiator concentration was increased which was also required to overcome the gradual ingress of oxygen into the PFA tubing which was quenching the reaction at low radical concentrations. Illdefined morphologies observed at PDAAm DPs close to the worm-vesicle boundary, combined with a peak in molar mass dispersity suggested poor mixing prevented an efficient morphological transition for these samples. However, by targeting higher PDAAm DPs, the additional monomer present during the transition plasticises the chains to facilitate formation of vesicles at PDAAm DPs of ≥300

Order-Order Morphological Transitions for Dual Stimulus Responsive Diblock Copolymer Vesicles

A series of non-ionic poly(glycerol monomethacrylate)− poly(2-hydroxypropyl methacrylate) (PGMA−PHPMA) diblock copolymer vesicles has been prepared by reversible addition−fragmentation chain transfer (RAFT) aqueous dispersion polymerization of HPMA at 70 °C at low pH using a carboxylic acid-based chain transfer agent. The degree of polymerization (DP) of the PGMA block was fixed at 43, and the DP of the PHPMA block was systematically varied from 175 to 250 in order to target vesicle phase space. Based on our recent work describing the analogous PGMA−PHPMA diblock copolymer worms [Lovett, J. R.; et al. Angew. Chem. 2015, 54, 1279−1283], such diblock copolymer vesicles were expected to undergo an order−order morphological transition via ionization of the carboxylic acid end-group on switching the solution pH. Indeed, irreversible vesicleto-sphere and vesicle-to-worm transitions were observed for PHPMA DPs of 175 and 200, respectively, as judged by turbidimetry, transmission electron microscopy (TEM), and dynamic light scattering (DLS) studies. However, such morphological transitions are surprisingly slow, with relatively long time scales (hours) being required at 20 °C. Moreover, no order−order morphological transitions were observed for vesicles comprising longer membrane-forming blocks (e.g., PGMA43− PHPMA225−250) on raising the pH from pH 3.5 to pH 6.0. However, in such cases the application of a dual stimulus comprising the same pH switch immediately followed by cooling from 20 to 5 °C, induces an irreversible vesicle-to-sphere transition. Finally, TEM and DLS studies conducted in the presence of 100 mM KCl demonstrated that the pH-responsive behavior arising from end-group ionization could be suppressed in the presence of added electrolyte. This is because charge screening suppresses the subtle change in the packing parameter required to drive the morphological transition

Enabling technologies in polymer synthesis: accessing a new design space for advanced polymer materials

This review discusses how developments in laboratory technologies can push the boundaries of what is achievable using existing polymer synthesis techniques. By making advances in reactor design, online monitoring and automation it has been possible to accelerate polymer discovery while achieving enhanced precision, reproducibility, safety and sustainability. It is hoped that gaining a broad understanding of what is achievable using new technologies will encourage a step-change in the way the polymer chemistry community approaches some aspects of research. This will hopefully open a new design space for the next generation of polymeric materials

A Facile Method for Generating Worm-like Micelles with Controlled Lengths and Narrow Polydispersity

This work shows that highly uniform worm micelles formed by polymerisation induced self-assembly can be obtained via simple postsynthesis sonication. Importantly, this straightforward and versatile strategy yields exceptionally monodisperse worms with tunable aspect ratios ranging from 7.2 to 17.6 by simply changing the sonication time

Steroid-Based Liquid Crystalline Polymers: Responsive and Biocompatible Materials of the Future

Steroid-based liquid crystal polymers and co-polymers have come a long way, with new and significant advances being made every year. This paper reviews some of the recent key developments in steroid-based liquid crystal polymers and co-polymers. It covers the structure–property relationship between cholesterol and sterol-based compounds and their corresponding polymers, and the influence of chemical structure and synthesis conditions on the liquid crystalline behaviour. An overview of the nature of self-assembly of these materials in solvents and through polymerisation is given. The role of liquid crystalline properties in the applications of these materials, in the creation of nano-objects, drug delivery and biomedicine and photonic and electronic devices, is discussed

A worm gel-based 3D model to elucidate the paracrine interaction between multiple myeloma and mesenchymal stem cells

Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells that develops mainly inside the bone marrow (BM) microenvironment. It is well known that autocrine and paracrine signals are responsible for the progression of this disease but the precise mechanism and contributions from single cell remain largely unknown. Mesenchymal stem cells (MSC) are an important cellular component of the BM: they support MM growth by increasing its survival and chemo-resistance, but little is known about the paracrine signaling pathways. Three-dimensional (3D) models of MM-MSC paracrine interactions are much more biologically-relevant than simple 2D models and are considered essential for detailed studies of MM pathogenesis. Herein we present a novel 3D co-culture model designed to mimic the paracrine interaction between MSC and MM cells. MSC were embedded within a previously characterized thermoresponsive block copolymer worm gel that can induce stasis in human pluripotent stem cells (hPSC) and then co-cultured with MM cells. Transcriptional phenotyping of co-cultured cells indicated the dysregulation of genes that code for known disease-relevant factors, and also revealed IL-6 and IL-10 as upstream regulators. Importantly, we have identified a synergistic paracrine signaling pathway between IL-6 and IL-10 that plays a critical role in sustaining MM cell proliferation. Our findings indicate that this 3D co-culture system is a useful model to investigate the paracrine interaction between MM cells and the BM microenvironment in vitro. This approach has revealed a new mechanism that promotes the proliferation of MM cells and suggested a new therapeutic target

Correction: Thermoresponsive polysarcosine-based nanoparticles

Correction for ‘Thermoresponsive polysarcosine-based nanoparticles’ by Huayang Yu et al., J. Mater. Chem. B, 2019, 7, 4217–4223

Linear ABC Amphiphilic Triblock Copolymers for Complexation and Protection of dsRNA

We herein report the synthesis and characterisation of linear ABC triblock copolymers, investigation of their self-assembly in aqueous solution, and complexation and protection with double stranded-RNA (dsRNA). The amphiphilic triblock copolymers were synthesised via reversible addition–fragmentation chain transfer (RAFT) polymerisation. The precisely controlled polymerisation allowed for modification of the degree of polymerisation of quaternised 2-(dimethylamino)ethyl methacrylate (QDMAEMA, Q), tert-butyl acrylamide (tBAA, B) and N,N-dimethyl acrylamide (DMA, D) blocks, tailoring hydrophobicity. The Q homopolymer was synthesised as a macromolecular chain-transfer agent. The cationic functionality provides the ability for electrostatic interaction of the triblock copolymers with anionic biomolecules, such as dsRNA, for therapeutic or agrochemical delivery applications. The B second block was designed to provide strong anchoring of the assembled structures for enhanced stability. As illustrated by 1H NMR spectroscopy, Q-b-B-b-D linear ABC triblock copolymers were prepared with molecular weights 30, 37 and 44 kDa. The self-assembly of these amphiphilic triblock copolymers in aqueous solution was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Furthermore, the potential of these tailored block copolymers as vehicles for dsRNA delivery was demonstrated through complexation and protection of the anionic biomolecule dsRNA against destabilisation at high salt concentration and enzymatic degradation by RNase A, confirmed by ethidium bromide exclusion and agarose gel electrophoresis assays

Exploiting breath figure reversibility for in situ pattern modulation and hierarchical design

The breath figure (BF) method employs condensation droplets as dynamic templates for patterning polymer films. In the classical approach, dropwise condensation and film solidification are simultaneously induced through solvent evaporation, leading to empirically derived patterns with limited predictability of the final design. Here we use the temporally arrested BF methodology, controlling condensation and polymerisation independently to create diverse BF patterns with varied pore size, arrangement and distribution. External temperature control enables us to further investigate and exploit the inherent reversibility of the phase change process that governs the pattern formation. We modulate the level of subcooling and superheating to achieve subsequent regimes of condensation and evaporation, permitting in situ regulation of the droplet growth and shrinkage kinetics. The full reversibility of the phase change processes joined with active photopolymerisation in the current approach thus allows arresting of predictable BF kinetics at intermediate stages, thereby accessing patterns with varied pore size and spacing for unchanged material properties and environmental conditions. This simultaneous active control over both the kinetics of phase change and polymer solidification offers affordable routes for the fabrication of diverse predictable porous surfaces; manufacture of monolithic hierarchical BF patterns are ultimately facilitated through the advanced control of the BF assembly using the method presented here

Recent Advances in Engineered Nanoparticles for RNAi-Mediated Crop Protection Against Insect Pests

Since the discovery of RNA interference (RNAi) in the nematode worm Caenorhabditis elegans in 1998 by Fire and Mello et al., strides have been made in exploiting RNAi for therapeutic applications and more recently for highly selective insect pest control. Although triggering mRNA degradation in insects through RNAi offers significant opportunities in crop protection, the application of environmental naked dsRNA is often ineffective in eliciting a RNAi response that results in pest lethality. There are many possible reasons for the failed or weak induction of RNAi, with predominant causes being the degradation of dsRNA in the formulated pesticide, in the field or in the insect once ingested, poor cuticular and oral uptake of the nucleic acid and sometimes the lack of an innate strong systemic RNAi response. Therefore, in the last 10 years significant research effort has focused on developing methods for the protection and delivery of environmental dsRNA to enable RNAi-induced insect control. This review focuses on the design and synthesis of vectors (vehicles that are capable of carrying and protecting dsRNA) that successfully enhance mRNA degradation via the RNAi machinery. The majority of solutions exploit the ability of charged polymers, both synthetic and natural, to complex with dsRNA, but alternative nanocarriers such as clay nanosheets and liposomal vesicles have also been developed. The various challenges of dsRNA delivery and the obstacles in the development of well-designed nanoparticles that act to protect the nucleic acid are highlighted. In addition, future research directions for improving the efficacy of RNA-mediated crop protection are anticipated with inspiration taken from polymeric architectures constructed for RNA-based therapeutic applications