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.magnified image

Amphiphilic diblock copolymers composed of two covalently linked, chemically distinct chains can be considered to be biological mimics of cell membrane-forming lipid molecules, but with typically more than an order of magnitude increase in molecular weight. These macromolecular amphiphiles are known to form a wide range of nanostructures (spheres, worms, vesicles, etc.) in solvents that are selective for one of the blocks. However, such self-assembly is usually limited to dilute copolymer solutions (<1%), which is a significant disadvantage for potential commercial applications such as drug delivery and coatings. In principle, this problem can be circumvented by polymerization-induced block copolymer self-assembly. Here we detail the synthesis and subsequent in situ self-assembly of amphiphilic AB diblock copolymers in a one pot concentrated aqueous dispersion polymerization formulation. We show that spherical micelles, wormlike micelles, and vesicles can be predictably and efficiently obtained (within 2 h of polymerization, >99% monomer conversion) at relatively high solids in purely aqueous solution. Furthermore, careful monitoring of the in situ polymerization by transmission electron microscopy reveals various novel intermediate structures (including branched worms, partially coalesced worms, nascent bilayers, "octopi", "jellyfish", and finally pure vesicles) that provide important mechanistic insights regarding the evolution of the particle morphology during the sphere-to-worm and worm-to-vesicle transitions. This environmentally benign approach (which involves no toxic solvents, is conducted at relatively high solids, and requires no additional processing) is readily amenable to industrial scale-up, since it is based on commercially available starting materials.

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.

The very low sliding friction at natural synovial joints, with friction coefficients µ < 0.002 at pressures up to 5 MPa or more, has not to date been attained in any man-made joints or between model surfaces in aqueous environments. We find that surfaces bearing grafted-from polyzwitterionic brushes in water can have µ values down to 0.0004 at pressures up to 7.5 MPa.This extreme lubrication is attributed primarily to the strong hydration of the phosphorylcholine-like monomers comprising the robustly-attached brushes, and may have relevance to a wide range of man-made aqueous lubrication situations. 3Rubbing of opposing bones during the articulation of mammalian joints is mediated by layers of articular cartilage coating their surfaces, which provide uniquely efficient lubrication as they slide past each other (1, 2). The associated very low friction at the high pressures of human joints such as hips or knees, with friction coefficients µ < 0.002, has not to date been emulated in man-made systems. Model studies (3-7) between smooth sliding surfaces bearing neutral or charged polymer brushes demonstrated sliding friction coefficients as low as µ < 0.001, values lower than with any other boundary lubricant system. As noted (8,9), in earlier studies with polymer brushes(3-6) the friction increases sharply at mean pressures P > ca. 0.3 MPa, which is far below the pressures, of 5 MPa or more, where low friction persists in nature. In the present work we sought to overcome the limitations of these earlier studies(3-6). We use polymer brushes, which make good boundary lubricants as they do not bridge the intersurface gap, that are strongly attached to each surface to resist being sheared off; and that are highly hydrated, to utilize the very efficient lubrication by hydration sheaths observed earlier(10, 11). 4 Figure 2 shows typical normal-force vs. surface separation profiles between pMPC brush-bearing mica surfaces in the standard crossed cylinder SFB configuration, in pure water and at salt concentrations ca. 0.01M and 0.1M NaNO 3 (the pMPC brush and monomer structure is inset to fig. 2A). Some contraction of the pMPC brushes is seen in the salt solutions relative to pure water. The highest normal loads F n applied are some 2 or more orders of magnitude higher than in earlier brush studies(4, 5) using the SFB. This leads to substantial flattening at the contact region, as indicated in the photo of the interference fringes, fig. 2B (and schematically in fig. 2C), from which the contact area A between the surfaces is measured directly (the mean pressures P across the flattened contact area are given by P = F n /A). Comparison with the control profiles from fig. 1A in the absence of polymer (dotted and broken curves in fig. 2A) reveals the extension of the unperturbed brushes from the macroinitiator layer, while fits to the force profiles provide more detailed information on the brush characteristics(12-section C, 13).We note the similarity of the profiles both on approach and separation of the surfaces (c...

Polymerization-induced self-assembly (PISA) of poly(glycerol monomethacrylate)–poly(2-hydroxypropyl methacrylate) (PGMA–PHPMA) diblocks is conducted using a RAFT aqueous dispersion polymerization formulation at 70 °C. Several PGMA macromolecular chain transfer agents (macro-CTAs) are chain-extended using a water-miscible monomer (HPMA): the growing PHPMA block becomes increasingly hydrophobic and hence drives in situ self-assembly. The final copolymer morphology in such PISA syntheses depends on just three parameters: the mean degree of polymerization (DP) of the PGMA stabilizer block, the mean DP of the PHPMA core-forming block, and the total solids concentration. Transmission electron microscopy is used to construct detailed diblock copolymer phase diagrams for PGMA DPs of 47, 78, and 112. For the shortest stabilizer block, there is essentially no concentration dependence: spheres, worms, or vesicles can be obtained even at 10% w/w solids simply by selecting the DP of the PHPMA block that gives the appropriate molecular curvature. For a PGMA DP of 78, the phase diagram is rich: and the copolymer morphology depends strongly on the total solids concentration. There is also a narrow region where spheres, worms, and vesicles coexist, which may be due to the effect of polydispersity. For a PGMA112 macro-CTA, the phase diagram is dominated by spherical morphologies. This is probably because the longer core-forming block DPs required to reduce the molecular curvature are significantly more dehydrated and hence less mobile, which prevents the in situ evolution of morphology from spheres to higher order morphologies. This hypothesis is supported by the observation that addition of ethanol to aqueous PISA syntheses conducted using the longer macro-CTAs allows access to diblock copolymer worms or vesicles, since this cosolvent solvates the core-forming PHPMA chains and hence increases their mobility at 70 °C. Elucidation of such phase diagrams is vital to ensure reproducible targeting of pure phases, rather than mixed phases.

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.

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.

Benzyl methacrylate (BzMA) is polymerized using a poly(lauryl methacrylate) macromolecular chain transfer agent (PLMA macro-CTA) using reversible addition–fragmentation chain transfer (RAFT) polymerization at 70 °C in n-dodecane. This choice of solvent leads to an efficient dispersion polymerization, with polymerization-induced self-assembly (PISA) occurring via the growing PBzMA block to produce a range of PLMA–PBzMA diblock copolymer nano-objects, including spheres, worms, and vesicles. In the present study, particular attention is paid to the worm phase, which forms soft free-standing gels at 20 °C due to multiple inter-worm contacts. Such worm gels exhibit thermo-responsive behavior: heating above 50 °C causes degelation due to the onset of a worm-to-sphere transition. Degelation occurs because isotropic spheres interact with each other much less efficiently than the highly anisotropic worms. This worm-to-sphere thermal transition is essentially irreversible on heating a dilute solution (0.10% w/w) but is more or less reversible on heating a more concentrated dispersion (20% w/w). The relatively low volatility of n-dodecane facilitates variable-temperature rheological studies, which are consistent with eventual reconstitution of the worm phase on cooling to 20 °C. Variable-temperature 1H NMR studies conducted in d26-dodecane confirm partial solvation of the PBzMA block at elevated temperature: surface plasticization of the worm cores is invoked to account for the observed change in morphology, because this is sufficient to increase the copolymer curvature and hence induce a worm-to-sphere transition. Small-angle X-ray scattering and TEM are used to investigate the structural changes that occur during the worm-to-sphere-to-worm thermal cycle; experiments conducted at 1.0 and 5.0% w/w demonstrate the concentration-dependent (ir)reversibility of these morphological transitions.