Polymerization-induced self-assembly and disassembly during the synthesis of thermoresponsive ABC triblock copolymer nano-objects in aqueous solution

Abstract

Polymerization-induced self-assembly (PISA) has been widely utilized as a powerful methodology for the preparation of various self-assembled AB diblock copolymer nano-objects in aqueous media. Moreover, it is well-documented that chain extension of AB diblock copolymer vesicles using a range of hydrophobic monomers via seeded RAFT aqueous emulsion polymerization produces framboidal ABC triblock copolymer vesicles with adjustable surface roughness owing to microphase separation between the two enthalpically incompatible hydrophobic blocks located within their membranes. However, the utilization of hydrophilic monomers for the chain extension of linear diblock copolymer vesicles has yet to be thoroughly explored; this omission is addressed for aqueous PISA formulations in the present study. Herein poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (G-H) vesicles were used as seeds for the RAFT aqueous dispersion polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Interestingly, this led to polymerization-induced disassembly (PIDA), with the initial precursor vesicles being converted into lower-order worms or spheres depending on the target mean degree of polymerization (DP) for the corona-forming POEGMA block. Moreover, construction of a pseudo-phase diagram revealed an unexpected copolymer concentration dependence for this PIDA formulation. Previously, we reported that PHPMA-based diblock copolymer nano-objects only exhibit thermoresponsive behavior over a relatively narrow range of compositions and DPs (see Warren et al., Macromolecules, 2018, 51, 8357-8371). However, introduction of the POEGMA coronal block produced thermoresponsive ABC triblock nano-objects even when the precursor G-H diblock copolymer vesicles proved to be thermally unresponsive. Thus, this new approach is expected to enable the rational design of new nano-objects with tunable composition, copolymer architectures and stimulus-responsive behavior.

Scheme 1. Schematic illustration of the synthesis route employed for the preparation of poly(glycerol monomethacrylate)₅₉-poly(2-hydroxypropyl methacrylate)₄₀₀ (G₅₉-H₄₀₀) diblock copolymer vesicles at 10–20% w/w solids via RAFT aqueous dispersion polymerization of HPMA using a G₅₉ precursor, and their subsequent utilization as seed particles for the preparation of G₅₉-H₄₀₀-O_x triblock copolymer nano-objects at 11–20% w/w solids via RAFT-mediated aqueous polymerization-induced disassembly (PIDA).

Fig. 1. Characterization of G₅₉-H₄₀₀ diblock copolymer precursor vesicles prepared via RAFT-mediated aqueous PISA when targeting (i) 10% w/w, (ii) 15% w/w or (iii) 20% w/w solids: (A) representative dry-state TEM images obtained using a 0.75% w/w uranyl formate staining solution; (B) corresponding representative cryo-TEM images; (C) membrane thickness distribution histograms and mean membrane thicknesses, determined by analyzing at least 100 vesicles in each case; (D) SAXS patterns recorded for 1.0% w/w aqueous vesicle dispersions.

Fig. 2. (A) Stacked ¹H NMR spectra (CD₃OD) recorded for a series of molecularly-dissolved G₅₉-H₄₀₀-O_x triblock copolymers (where x = 35, 70, 100, 200 or 350) prepared via RAFT-mediated aqueous PIDA at 15% w/w solids. (B) Normalized SEC traces (refractive index detector) recorded for the G₅₉ precursor (black line), the G₅₉-H₄₀₀ diblock copolymer (red line) and a series of G₅₉-H₄₀₀-O_x triblock copolymers (where x = 35, blue line; x = 70, green line; x = 100, purple line; x = 200, orange line; x = 350, burgundy line) at 15% w/w solids (DMF + 10 mM LiBr eluent).

Fig. 3. Pseudo-phase diagram constructed for G₅₉-H₄₀₀-O_x triblock copolymer nano-objects (x = 35–350) prepared via RAFT-mediated aqueous PIDA by systematically varying the total solids content and target POEGMA DP. Representative TEM images obtained using a 0.75% w/w uranyl formate staining solution are shown for each formulation. Each frame color corresponds to a different nano-object morphology (S = spherical micelles; W = worms; J = jellyfish and V = vesicles).

Fig. 4. (A) OEGMA conversion vs. time curve (black circles) and corresponding ln([M]₀/[M]) vs. time plot (red circles) determined by ¹H NMR spectroscopy studies (CD₃OD) during the synthesis of G₅₉-H₄₀₀-O₃₅₀ triblock copolymer spheres via RAFT-mediated aqueous PIDA at 37 °C targeting 15% w/w solids. (B) Evolution in M_n (black circles) and M_w/M_n (red circles) with OEGMA conversion for a series of G₅₉-H₄₀₀-O_x triblock copolymers prepared at 15% w/w solids, as calculated from SEC analysis (refractive index detector) using a series of PMMA calibration standards (DMF eluent + 10 mM LiBr). (C) Representative TEM images recorded for G₅₉-H₄₀₀-O_x triblock copolymer nano-objects formed during the synthesis of G₅₉-H₄₀₀-O₃₅₀ triblock copolymer spheres via RAFT-mediated aqueous PIDA at 37 °C targeting 15% w/w solids, obtained using a uranyl formate stain. The polymerization time, OEGMA conversion and corresponding POEGMA DP are indicated for each image.

Fig. 5. Characterization data obtained for (i) G₅₉-H₄₀₀ diblock copolymer vesicles, (ii) G₅₉-H₄₀₀-O₃₅ triblock copolymer nano-objects, and (iii) G₅₉-H₄₀₀-O₂₀₀ triblock copolymer nano-objects at 25 °C (red data) and 5 °C (blue data) after incubation at each temperature for 24 h prior to analysis: (A) intensity-weighted particle size distributions, mean D_h values and polydispersities determined by DLS analysis of 0.1% w/w aqueous dispersions (the error indicates the standard deviation from at least three repeat measurements). (B) Representative TEM images obtained using a uranyl formate stain. (C) SAXS patterns recorded for 1.0% w/w aqueous dispersions. (D) Complex viscosity (|η*|) as a function of applied strain (insets show digital images recorded for the corresponding aqueous copolymer dispersions at 10–11% w/w solids, which indicate whether they form a free-standing gel or a free-flowing fluid in each case).