Polymerization-induced self-assembly of block copolymer nano-objects via RAFT aqueous dispersion polymerization

Abstract

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.

Scheme 1. Principle of Polymerization-Induced Self-Assembly Conducted in Aqueous Media

A water-soluble stabilizer block is chain-extended using a water-miscible monomer via RAFT polymerization. Initially, a soluble diblock copolymer is obtained, but at some critical degree of polymerization the growing second block becomes water-insoluble, which causes in situ self-assembly. In this case only a spherical morphology is depicted, but other morphologies are also possible (see later).

Scheme 2. Chemical Structures of Five Water-Miscible Vinyl Monomers for Which Each Corresponding Homopolymer Is Water-Insoluble

Such monomers form a relatively small subset of building blocks that fulfill the essential requirements for an aqueous dispersion polymerization formulation.

Figure 1

(a) Synthesis of spherical diblock copolymer nanogels via RAFT aqueous dispersion polymerization at 30 or 40 °C. (b) Intensity average size distribution obtained using DLS. (c) AFM image of the dried nanogel particles. Adapted with permission from ref (41).

Figure 2

RAFT aqueous dispersion polymerization of 2-hydroxypropyl methacrylate using either a poly(glycerol monomethacrylate), poly[2-(methacryloyloxy)ethyl phosphorylcholine], or poly(ethylene glycol) macromolecular chain transfer agent to produce spheres, worms, or vesicles by judicious variation of the packing parameter, P, which is determined by the relative volume fractions of the stabilizer and core-forming blocks.

Figure 3

Representative transmission electron microscopy (TEM) images obtained for (a–c) a series of G₁₁₂-H_x spheres; (d–f) G₇₈-H_x spheres, worms, and vesicles synthesized at various concentrations; (g) M₅₀-(H₄₀₀-E₆) “lumpy rods”; (h) PEG₁₁₃-PHPMA₃₀₀ oligolamellar vesicles; and (i) G₅₅-H₃₀₀-B₃₀₀ framboidal vesicles. Scale bar on inset images = 200 nm. For brevity, G, H, M, E, and B denote GMA, HPMA, MPC, EGDMA, and BzMA, respectively. Adapted with permission from refs (43), (52), and (70).

Figure 4

(a) HPMA polymerization kinetics obtained for the targeted G₄₇-H₂₀₀ diblock copolymer nanoparticles (where G and H are shorthand for GMA and HPMA, respectively) prepared via RAFT aqueous dispersion polymerization at 70 °C and 10% w/w solids. According to TEM studies, the five morphological regimes are as follows: molecularly dispersed copolymer chains (M), spherical micelles (S), worms (W), branched worms (BW), jellyfish (J), and vesicles (V). The inset shows a semilogarithmic plot for a subset of these data, which confirms the five-fold nucleation-induced rate enhancement observed after micellar aggregation. (b) TEM image of spherical micelles at 46% HPMA conversion. (c) TEM image of worms at 62% HPMA conversion (scale bar = 100 nm). (d) Suggested mechanism for the worm-to-vesicle transformation during the synthesis of G₄₇-H₂₀₀ by RAFT aqueous dispersion polymerization. Adapted with permission from ref (42).

Figure 5

Phase diagrams obtained for a series of (a) G₇₈-H_x and (b) G₄₇-H_x copolymers synthesized by aqueous RAFT dispersion polymerization over copolymer concentrations ranging from 10% to 25% w/w. S = spherical micelles, W = worms, BW = branched worms, and V = vesicles. Adapted with permission from ref (43).

Figure 6

(a) Thermoresponsive aqueous solution behavior of a 10% w/w aqueous dispersion of G₅₄-H₁₄₀ diblock copolymer particles. TEM studies of grids prepared from a dilute aqueous dispersion of G₅₄-H₁₄₀ dried at either 21 or 4 °C showing the reversible worm-to-sphere transition. (b) Variation of storage (G′, filled symbols) and loss (G″, open symbols) moduli for a G₅₄-H₁₄₀ worm gel at 10 w/w % during temperature cycling at 1 °C min^–1: (i) cooling from 25 to 2 °C (G′, filled red squares; G″, open black circles) and (ii) subsequent warming from 2 to 25 °C (G′, filled blue triangles; G″, open green diamonds). (c) Small-angle X-ray scattering (SAXS) patterns recorded for a 10% w/w G₅₄-H₁₄₀ aqueous dispersion, confirming the reversible nature of the worm-to-sphere transition after two consecutive temperature cycles between 5 and 25 °C. These SAXS plots overlay almost perfectly, indicating excellent reversibility for this thermal transition. The dashed curve shows a simulated SAXS pattern of long cylindrical rods (diameter = 22 nm, diameter polydispersity = 18%, mean length = 1000 nm) which is given for comparison with the experimental SAXS data obtained for worms. (d) Fluorescence observed before and after sterilization by ultrafiltration of an aqueous dispersion of G₅₄-H₁₄₀ diblock copolymer after its deliberate contamination with FITC-labeled S. aureus. (e) Plate cultures of unfiltered and ultrafiltered copolymer gels obtained after incubation for 24 h at 37 °C. Clearly, substantial bacterial growth has occurred in the unfiltered copolymer gel. In contrast, no bacterial growth is observed for the ultrafiltered copolymer gel (right-hand image), indicating complete removal of S. aureus. Adapted with permission from ref (51).

Figure 7

(a) Synthesis of a G₅₈-H₃₅₀-B₄₀₀ triblock copolymer (where G, H, and B denote GMA, HPMA, and BzMA, respectively) via RAFT seeded emulsion polymerization of benzyl methacrylate from a G₅₈-H₃₅₀ diblock precursor prepared by RAFT aqueous dispersion polymerization. (b) Evolution of morphology from conventional G₅₈-H₃₅₀ vesicles to framboidal G₅₈-H₃₅₀-B₄₀₀ vesicles. (c) Representative DMF GPC curves recorded for the G₅₈ macro-CTA, G₅₈-H₃₅₀ diblock and G₅₈-H₃₅₀-B₄₀₀triblock. Adapted with permission from ref (70).

Figure 8

(a) Schematic representation of the preparation of Pickering emulsions using cross-linked G₅₈-H₃₅₀-E₂₀ vesicles. (b) TEM image of cross-linked vesicles. (c) Fluorescence micrograph of colloidosomes obtained from a Pickering emulsion precursor prepared using fluorescein-labeled vesicles. Adapted with permission from ref (74).

Figure 9

RAFT aqueous dispersion polymerization of HPMA using a binary mixture of PKSPMA₃₄ and PGMA₆₀ macro-CTAs to produce anionic diblock copolymer nano-objects. Adapted with permission from ref (87).

Figure 10

Transmission electron micrographs obtained for (a) a typical jellyfish intermediate observed during the synthesis of PGMA₄₇-PHPMA₂₀₀ vesicles via RAFT PISA at 70 °C (adapted with permission from ref (42)) and (b) a similar species observed during the post-polymerization processing of a PMPC₂₅-PDPA₁₃₅ diblock copolymer via a solvent switch at 20 °C. The striking similarities between these structures suggest that such jellyfish are generic intermediates, rather than being merely an esoteric feature of the PISA process.