Steven P. Armes

Self‐Assembled Block Copolymer Aggregates: From Micelles to Vesicles and their Biological Applications

The ability of amphiphilic block copolymers to self-assemble in selective solvents has been widely studied in academia and utilized for various commercial products. The self-assembled polymer vesicle is at the forefront of this nanotechnological revolution with seemingly endless possible uses, ranging from biomedical to nanometer-scale enzymatic reactors. This review is focused on the inherent advantages in using polymer vesicles over their small molecule lipid counterparts and the potential applications in biology for both drug delivery and synthetic cellular reactors.

Synthesis and aqueous solution properties of near-monodisperse tertiary amine methacrylate homopolymers and diblock copolymers

Group transfer polymerisation (GTP) of four tertiary amine methacrylates, 2-(dimethylamino)ethyl methacrylate (DMA), 2-(diethylamino)ethyl methacrylate (DEA), 2-(diisopropylamino)ethyl methacrylate (DPA) and 2-(N-morpholino)ethyl methacrylate (MEMA) produced a series of near-monodisperse homopolymers (Mw/Mn<1.15). Molecular weights were controlled by varying the monomer/initiator ratio. The DMA and MEMA homopolymers were both water-soluble at 20°C in acidic or neutral media. Inverse temperature solubility behaviour was observed at higher temperatures, with cloud-points ranging from 32 to 53°C at pH 8. The Cloud-points decreased monotonically with increasing degrees of polymerisation, as expected. The MEMA homopolymers were particularly sensitive to the added electrolyte, with ‘salting out’ occurring at 20°C on addition of 0.2–0.3 M Na2SO4. The more hydrophobic DEA and DPA homopolymers were both insoluble at 20°C and neutral pH but readily dissolved as cationic polyelectrolytes in acidic media due to protonation of the tertiary amine residues. In addition, DMA was block copolymerized in turn with each of the other three tertiary amine methacrylate comonomers. These diblock copolymers could be dissolved molecularly without co-solvents in aqueous media at 20°C, with micellization occurring reversibly on judicious adjustment of the solution pH, temperature or electrolyte concentration. In all three cases, stable block copolymer micelles were formed with DMA coronas and hydrodynamic diameters of 20–60 nm.

Lubrication at Physiological Pressures by Polyzwitterionic Brushes

The very low sliding friction at natural synovial joints, which have friction coefficients of μ < 0.002 at pressures up to 5 megapascals or more, has to date not been attained in any human-made joints or between model surfaces in aqueous environments. We found that surfaces in water bearing polyzwitterionic brushes that were polymerized directly from the surface can have μ values as low as 0.0004 at pressures as high as 7.5 megapascals. This extreme lubrication is attributed primarily to the strong hydration of the phosphorylcholine-like monomers that make up the robustly attached brushes, and may have relevance to a wide range of human-made aqueous lubrication situations.

Polymerization-Induced Self-Assembly of Block Copolymer Nano-objects via RAFT Aqueous Dispersion Polymerization

In this Perspective, we discuss the recent development of polymerization-induced self-assembly mediated by reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization. This approach has quickly become a powerful and versatile technique for the synthesis of a wide range of bespoke organic diblock copolymer nano-objects of controllable size, morphology, and surface functionality. Given its potential scalability, such environmentally-friendly formulations are expected to offer many potential applications, such as novel Pickering emulsifiers, efficient microencapsulation vehicles, and sterilizable thermo-responsive hydrogels for the cost-effective long-term storage of mammalian cells.

Aqueous Dispersion Polymerization: A New Paradigm for in Situ Block Copolymer Self-Assembly in Concentrated Solution

Reversible addition-fragmentation chain transfer polymerization has been utilized to polymerize 2-hydroxypropyl methacrylate (HPMA) using a water-soluble macromolecular chain transfer agent based on poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC). A detailed phase diagram has been elucidated for this aqueous dispersion polymerization formulation that reliably predicts the precise block compositions associated with well-defined particle morphologies (i.e., pure phases). Unlike the ad hoc approaches described in the literature, this strategy enables the facile, efficient, and reproducible preparation of diblock copolymer spheres, worms, or vesicles directly in concentrated aqueous solution. Chain extension of the highly hydrated zwitterionic PMPC block with HPMA in water at 70 °C produces a hydrophobic poly(2-hydroxypropyl methacrylate) (PHPMA) block, which drives in situ self-assembly to form well-defined diblock copolymer spheres, worms, or vesicles. The final particle morphology obtained at full monomer conversion is dictated by (i) the target degree of polymerization of the PHPMA block and (ii) the total solids concentration at which the HPMA polymerization is conducted. Moreover, if the targeted diblock copolymer composition corresponds to vesicle phase space at full monomer conversion, the in situ particle morphology evolves from spheres to worms to vesicles during the in situ polymerization of HPMA. In the case of PMPC(25)-PHPMA(400) particles, this systematic approach allows the direct, reproducible, and highly efficient preparation of either block copolymer vesicles at up to 25% solids or well-defined worms at 16-25% solids in aqueous solution.

Optimum reaction conditions for the polymerization of pyrrole by iron(III) chloride in aqueous solution

Abstract The optimum initial mole ratio of iron(III)/pyrrole for the polymerization by aqueous iron(III) chloride solution at 19°C is shown to be approximately 2.38 ± 0.04. Thus the number of electrons transferred per pyrrole ring in the chemical synthesis of polypyrrole is consistent with values quoted for various electrochemical syntheses. It is shown that changing the initial mole ratio of the reactants affects the yield but not the chemical composition or conductivity of the polypyrrole powders. The extent of reaction as a function of time at two different reactant concentrations is also presented.

RAFT synthesis of sterically stabilized methacrylic nanolatexes and vesicles by aqueous dispersion polymerization.

Emulsion polymerization is widely used for waterborne coatings. Reducing the latex particle size is known to promote coalescence and hence enhance film formation. However, the synthesis of smaller latexes usually requires additional surfactant, which can compromise the quality of waterborne coatings (e.g. poor adhesion and reduced film quality due to migration of excess surfactant). In principle, reactive surfactants offer a potentially decisive advantage over conventional surfactants in emulsion polymerization because they bind irreversibly to the latex and hence cannot migrate during film formation; this allows defect-free coatings to be produced with reduced moisture sensitivity. Over the last two decades, controlled/living radical polymerization techniques have become powerful tools in polymer synthesis. There are many examples of latex syntheses based on these approaches. For example, nitroxide-mediated living radical polymerization has been used by Charleux, El-Aasser, Okubo, and Georges to mediate the miniemulsion polymerization of n-butyl acrylate and styrene. ATRP has been optimized by Matyjaszewski and Okubo for the (mini)emulsion polymerization of (meth)acrylic and styrene monomers. Reversible addition– fragmentation chain transfer (RAFT) polymerization has been extensively exploited in the context of both emulsion and miniemulsion polymerization by Hawkett, Charleux, El-Aasser, Cunningham, and Zhu. There are also a number of RAFT syntheses conducted under nonaqueous dispersion polymerization conditions. However, as far as we are aware, there are only three examples of the application of controlled/living radical polymerization techniques for latex syntheses by aqueous dispersion polymerization. In each case, a relatively expensive speciality monomer was utilized for the latex core, namely N-isopropylacrylamide or N,N’-diethylacrylamide. This relative lack of research is perhaps surprising, because aqueous dispersion polymerization is conceptually much simpler than aqueous emulsion polymerization since the initial reaction solution is homogeneous in the former case. Presumably, the paucity of experimental data merely reflects the fact that there are relatively few vinyl monomers that are suitable for latex syntheses by aqueous dispersion polymerization. Recently, we reported the use of conventional (nonliving) free radical chemistry for the aqueous dispersion polymerization of a commodity methacrylic monomer, 2hydroxypropyl methacrylate (HPMA). The resulting PHPMA latexes were stabilized by poly(N-vinylpyrrolidone) and the mean particle diameter could be varied from approximately 100 to 1000 nm diameter, with good control over the particle size distribution being achieved in most cases. Herein we explore the RAFT synthesis of sterically stabilized PHPMA nanolatexes of 20 to 100 nm diameter by surfactant-free aqueous dispersion polymerization using a poly(glycerol monomethacrylate)-based chain transfer agent (CTA) as the reactive steric stabilizer. Thus both the latex cores and the steric stabilizer chains of the resulting nanolatexes are highly hydroxylated for this prototype formulation. Moreover, varying the length of the targeted PHPMA chains allows the final size of the sterically stabilized nanolatex particles to be controlled quite precisely (see Scheme 1, Table 1, and the Supporting Information).

Sterilizable Gels from Thermoresponsive Block Copolymer Worms

Biocompatible hydrogels have many applications, ranging from contact lenses to tissue engineering scaffolds. In most cases, rigorous sterilization is essential. Herein we show that a biocompatible diblock copolymer forms wormlike micelles via polymerization-induced self-assembly in aqueous solution. At a copolymer concentration of 10.0 w/w %, interworm entanglements lead to the formation of a free-standing physical hydrogel at 21 °C. Gel dissolution occurs on cooling to 4 °C due to an unusual worm-to-sphere order-order transition, as confirmed by rheology, electron microscopy, variable temperature (1)H NMR spectroscopy, and scattering studies. Moreover, this thermo-reversible behavior allows the facile preparation of sterile gels, since ultrafiltration of the diblock copolymer nanoparticles in their low-viscosity spherical form at 4 °C efficiently removes micrometer-sized bacteria; regelation occurs at 21 °C as the copolymer chains regain their wormlike morphology. Biocompatibility tests indicate good cell viabilities for these worm gels, which suggest potential biomedical applications.

A Schizophrenic Water-Soluble Diblock Copolymer

Two micellar states are possible for a novel PPO-PDEA diblock copolymer synthesized by atom-transfer radical polymerization. Subtle variation of the solution pH value and temperature is all that is needed to form both conventional micelles (with the PDEA block in the core) and reverse micelles (with the PPO block in the core) in aqueous media (shown schematically). DEA=2-(diethylamino)ethyl methacrylate, PO=propylene oxide.

Controlling Cellular Uptake by Surface Chemistry, Size, and Surface Topology at the Nanoscale

Cell cytosol and the different subcellular organelles house the most important biochemical processes that control cell functions. Effective delivery of bioactive agents within cells is expected to have an enormous impact on both gene therapy and the future development of new therapeutic and/or diagnostic strategies based on single-cell-bioactive-agent interactions. Herein a biomimetic nanovector is reported that is able to enter cells, escape from the complex endocytic pathway, and efficiently deliver actives within clinically relevant cells without perturbing their metabolic activity. This nanovector is based on the pH-controlled self-assembly of amphiphilic copolymers into nanometer-sized vesicles (or polymersomes). The cellular-uptake kinetics can be regulated by controlling the surface chemistry, the polymersome size, and the polymersome surface topology. The latter is controlled by the extent of polymer-polymer phase separation within the external envelope of the polymersome.