RAFT dispersion polymerization of glycidyl methacrylate for the synthesis of epoxy-functional block copolymer nanoparticles in mineral oil

Epoxy-functional poly(stearyl methacrylate)-poly(glycidyl methacrylate) (PSMA-PGlyMA) diblock copolymer nanoparticles are synthesized via reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of glycidyl methacrylate (GlyMA) in mineral oil at 70 °C. This efficient polymerization-induced self-assembly (PISA) formulation yields well-defined spheres of tunable diameter as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. 1H NMR spectroscopy and gel permeation chromatography (GPC) studies indicate that such non-polar dispersions exhibit greater stability during their long-term storage at 20 °C compared to related epoxy-functional nanoparticles prepared via RAFT aqueous emulsion polymerization. Model epoxy-amine ring-opening reactions using N-methylaniline demonstrate the potential for post-polymerization functionalization of such spherical nanoparticles

Cellular delivery of antibodies: effective targeted subcellular imaging and new therapeutic tool

It is already more than a century since the pioneering work of the Nobel Laureate Ehrlich gave birth to the side chain theory1, which helped to define antibodies and their ability to target specific biological sites. However, the use of antibodies is still restricted to the extracellular space due to the lack of a suitable delivery vehicle for the efficient transport of antibodies into live cells without inducing toxicity. In this work, we report the efficient encapsulation and delivery of antibodies into live cells with no significant loss of cell viability or any deleterious affect on the cell metabolic activity. This delivery system is based on poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-(2-(diisopropylamino)ethyl methacrylate), (PMPC-PDPA), a pH sensitive diblock copolymer that self-assembles to form nanometer-sized vesicles, also known as polymersomes, at physiological pH. These polymersomes can successfully deliver relatively high antibody payloads within live cells. Once inside the cells, we demonstrate that these antibodies can target their epitope by immune-labelling of cytoskeleton, Golgi, and transcription factor proteins in live cells. We also demonstrate that this effective antibody delivery mechanism can be used to control specific subcellular events, as well as modulate cell activity and pro-inflammatory process

Block Copolymer Nanoparticles Prepared via Polymerization-Induced Self-Assembly Provide Excellent Boundary Lubrication Performance for Next-Generation Ultralow-Viscosity Automotive Engine Oils

Core cross-linked poly(stearyl methacrylate)–poly(benzyl methacrylate)–poly(ethylene glycol dimethacrylate) [S31–B200–E20] triblock copolymer nanoparticles were synthesized directly in an industrial mineral oil via polymerization-induced self-assembly (PISA). Gel permeation chromatography analysis of the S31–B200 diblock copolymer precursor chains indicated a well-controlled reversible addition–fragmentation chain transfer dispersion polymerization, while transmission electron microscopy, dynamic light-scattering (DLS), and small-angle X-ray scattering studies indicated the formation of well-defined spheres. Moreover, DLS studies performed in THF, which is a common solvent for the S and B blocks, confirmed successful covalent stabilization because well-defined solvent-swollen spheres were obtained under such conditions. Tribology experiments using a mini-traction machine (MTM) indicated that 0.50% w/w dispersions of S31–B200–E20 spheres dramatically reduce the friction coefficient of base oil within the boundary lubrication regime. Given their efficient and straightforward PISA synthesis at high solids, such nanoparticles offer new opportunities for the formulation of next-generation ultralow-viscosity automotive engine oils

Synthesis of well-defined epoxy-functional spherical nanoparticles by RAFT aqueous emulsion polymerization

The environmentally-friendly synthesis of epoxy-functional spherical nanoparticles has been achieved using polymerization-induced self-assembly (PISA) in aqueous solution. Firstly, a non-ionic hydrophilic stabilizer block, poly(glycerol monomethacrylate) (PGMA), was prepared by reversible addition–fragmentation chain transfer (RAFT) solution polymerization in ethanol. This water-soluble precursor was subsequently chain-extended via RAFT aqueous emulsion polymerization of glycidyl methacrylate (GlyMA) at 50 °C and neutral pH to ensure maximum retention of the epoxy functionality. PISA leads to the formation of well-defined PGMA-PGlyMA spherical diblock copolymer nanoparticles at up to 35% w/w solids and 1H NMR spectroscopy studies indicated that virtually all of the epoxy groups survive such relatively mild conditions. DMF GPC studies confirmed that relatively low dispersities (Mw/Mn </p

Exploring the Upper Size Limit for Sterically Stabilized Diblock Copolymer Nanoparticles Prepared by Polymerization-Induced Self-Assembly in Non-Polar Media

Reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate is used to prepare a series of well-defined poly(stearyl methacrylate)–poly(benzyl methacrylate) (PSMA–PBzMA) diblock copolymer nanoparticles in mineral oil at 90 °C. A relatively long PSMA54 precursor acts as a steric stabilizer block and also ensures that only kinetically trapped spheres are obtained, regardless of the target degree of polymerization (DP) for the core-forming PBzMA block. This polymerization-induced self-assembly (PISA) formulation provides good control over the particle size distribution over a wide size range (24–459 nm diameter). 1H NMR spectroscopy studies confirm that high monomer conversions (≥96%) are obtained for all PISA syntheses while transmission electron microscopy and dynamic light scattering analyses show well-defined spheres with a power-law relationship between the target PBzMA DP and the mean particle diameter. Gel permeation chromatography studies indicate a gradual loss of control over the molecular weight distribution as higher DPs are targeted, but well-defined morphologies and narrow particle size distributions can be obtained for PBzMA DPs up to 3500, which corresponds to an upper particle size limit of 459 nm. Thus, these are among the largest well-defined spheres with reasonably narrow size distributions (standard deviation ≤20%) produced by any PISA formulation. Such large spheres serve as model sterically stabilized particles for analytical centrifugation studies

Antimicrobial graft copolymer gels

In view of the growing worldwide rise in microbial resistance, there is considerable interest in designing new antimicrobial copolymers. The aim of the current study was to investigate the relationship between antimicrobial activity and copolymer composition/ architecture to gain a better understanding of their mechanism of action. Specifically, the antibacterial activity of several copolymers based on 2- (methacryloyloxy)ethyl phosphorylcholine [MPC] and 2-hydroxypropyl methacrylate (HPMA) toward Staphylococcus aureus was examined. Both block and graft copolymers were synthesized using either atom transfer radical polymerization or reversible addition−fragmentation chain transfer polymerization and characterized via 1H NMR, gel permeation chromatography, rheology, and surface tensiometry. Antimicrobial activity was assessed using a range of well-known assays, including direct contact, live/dead staining, and the release of lactate dehydrogenase (LDH), while transmission electron microscopy was used to study the morphology of the bacteria before and after the addition of various copolymers. As expected, PMPC homopolymer was biocompatible but possessed no discernible antimicrobial activity. PMPC-based graft copolymers comprising PHPMA side chains (i.e. PMPC-g-PHPMA) significantly reduced both bacterial growth and viability. In contrast, a PMPC−PHPMA diblock copolymer comprising a PMPC stabilizer block and a hydrophobic core-forming PHPMA block did not exhibit any antimicrobial activity, although it did form a biocompatible worm gel. Surface tensiometry studies and LDH release assays suggest that the PMPC-g-PHPMA graft copolymer exhibits surfactantlike activity. Thus, the observed antimicrobial activity is likely to be the result of the weakly hydrophobic PHPMA chains penetrating (and hence rupturing) the bacterial membrane

Long-Term Stability of n-Alkane-in-Water Pickering Nanoemulsions: Effect of Aqueous Solubility of Droplet Phase on Ostwald Ripening

High-pressure microfluidization is used to prepare a series of oil-in-water Pickering nanoemulsions using sterically-stabilized diblock copolymer nanoparticles as the Pickering emulsifier. The droplet phase comprised either n-octane, n-decane, n-dodecane, or n-tetradecane. This series of oils enabled the effect of aqueous solubility on Ostwald ripening to be studied, which is the primary instability mechanism for such nanoemulsions. Analytical centrifugation (LUMiSizer instrument) was used to evaluate the long-term stability of these Pickering nanoemulsions over time scales of weeks/months. This technique enables convenient quantification of the fraction of growing oil droplets and confirmed that using n-octane (aqueous solubility = 0.66 mg dm–3 at 20 °C) leads to instability even over relatively short time periods. However, using n-tetradecane (aqueous solubility = 0.386 μg dm–3 at 20 °C) leads to significantly improved long-term stability with respect to Ostwald ripening, with all droplets remaining below 1 μm diameter after 6 weeks storage at 20 °C. In the case of n-dodecane, the long-term stability of these new copolymer-stabilized Pickering nanoemulsions is significantly better than the silica-stabilized Pickering nanoemulsions reported in the literature by Persson et al. (Colloids Surf., A,2014,459, 48–57). This is attributed to a much greater interfacial yield stress for the former system, as recently described in the literature (see P. J. Betramo et al. Proc. Natl. Acad. Sci. U.S.A.,2017,114, 10373–10378)

A Single Thermoresponsive Diblock Copolymer Can Form Spheres, Worms or Vesicles in Aqueous Solution

It is well‐known that the self‐assembly of AB diblock copolymers in solution can produce various morphologies depending on the relative volume fraction of each block. Recently, polymerization‐induced self‐assembly (PISA) has become widely recognized as a powerful platform technology for the rational design and efficient synthesis of a wide range of block copolymer nano‐objects. In this study, PISA is used to prepare a new thermoresponsive poly(N‐(2‐hydroxypropyl) methacrylamide)‐poly(2‐hydroxypropyl methacrylate) [PHPMAC‐PHPMA] diblock copolymer. Remarkably, TEM, rheology and SAXS studies indicate that a single copolymer composition can form well‐defined spheres (4 °C), worms (22 °C) or vesicles (50 °C) in aqueous solution. Given that the two monomer repeat units have almost identical chemical structures, this system is particularly well‐suited to theoretical analysis. Self‐consistent mean field theory suggests this rich self‐assembly behavior is the result of the greater degree of hydration of the PHPMA block at lower temperature, which is in agreement with variable temperature 1H NMR studies

Shear-Induced Alignment of Block Copolymer Worms in Mineral Oil

Poly(stearyl methacrylate)-poly(benzyl methacrylate) [PSMA-PBzMA] diblock copolymer worms were synthesized directly in mineral oil via reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization at 90 °C. Free-standing gels were obtained from this polymerization-induced self-assembly (PISA) formulation when targeting PSMA13-PBzMA65 dispersions at 5% w/w to 20% w/w copolymer concentration. Gel permeation chromatography (GPC) studies indicated that almost identical copolymer chains were obtained in all cases, while transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) studies confirmed that highly anisotropic worms were formed with mean cross-sectional diameters of 11.9-13.1 nm. These worms undergo a thermoreversible worm-to-sphere transition on heating up to 150 °C. Rheological studies were conducted to characterize the shear rate- and concentration-dependent behaviour caused by this change in copolymer morphology, where the initial shear-thinning worm gels form spheres (i.e. a Newtonian fluid) on heating up to 150 °C. Complementary shear-induced polarized light imaging (SIPLI) experiments confirmed the formation of aligned linear worms under applied shear between 80 °C and 110 °C, with high-viscosity dispersions of branched worms being obtained at 20-60 °C and low-viscosity spheres being produced at 150 °C. This study informs the use of such block copolymer worms as rheology modifiers for non-polar oils, which is of potential interest for the automotive industry

Evidence of ratchet effect in nanowires of a conducting polymer

Ratchet effect, observed in many systems starting from living organism to artificially designed device, is a manifestation of motion in asymmetric potential. Here we report results of a conductivity study of Polypyrrole nanowires, which have been prepared by a simple method to generate a variation of doping concentration along the length. This variation gives rise to an asymmetric potential profile that hinders the symmetry of the hopping process of charges and hence the value of measured resistance of these nanowires become sensitive to the direction of current flow. The asymmetry in resistance was found to increase with decreasing nanowire diameter and increasing temperature. The observed phenomena could be explained with the assumption that the spatial extension of localized state involved in hopping process reduces as the doping concentration reduces along the length of the nanowires.Comment: Revtex, two column, 4 pages, 10 figure