Polymerization-induced self-assembly (PISA) is a powerful platform technology for the rational and efficient synthesis of a wide range of block copolymer nano-objects (e.g., spheres, worms or vesicles) in various media. In situ small-angle X-ray scattering (SAXS) studies of reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization have previously provided detailed structural information during self-assembly (see 30155157 Chem. Sci. 2016 7 5078 5090 ). However, conducting the analogous in situ SAXS studies during RAFT aqueous emulsion polymerizations poses a formidable technical challenge because the inherently heterogeneous nature of such PISA formulations requires efficient stirring to generate sufficiently small monomer droplets. In the present study, the RAFT aqueous emulsion polymerization of 2-methoxyethyl methacrylate (MOEMA) has been explored for the first time. Chain extension of a relatively short non-ionic poly(glycerol monomethacrylate) (PGMA) precursor block leads to the formation of sterically-stabilized PGMA-PMOEMA spheres, worms or vesicles, depending on the precise reaction conditions. Construction of a suitable phase diagram enables each of these three morphologies to be reproducibly targeted at copolymer concentrations ranging from 10 to 30% w/w solids. High MOEMA conversions are achieved within 2 h at 70 °C, which makes this new PISA formulation well-suited for in situ SAXS studies using a new reaction cell. This bespoke cell enables efficient stirring and hence allows in situ monitoring during RAFT emulsion polymerization for the first time. For example, the onset of micellization and subsequent evolution in particle size can be studied when preparing PGMA 29 -PMOEMA 30 spheres at 10% w/w solids. When targeting PGMA 29 -PMOEMA 70 vesicles under the same conditions, both the micellar nucleation event and the subsequent evolution in the diblock copolymer morphology from spheres to worms to vesicles are observed. These new insights significantly enhance our understanding of the PISA mechanism during RAFT aqueous emulsion polymerization.

Infected diabetic wounds are difficult to heal due to high reactive oxygen species (ROS) concentrations and recurrent infections. Such wounds can easily deteriorate into a diabetic ulcer, a chronic diabetic complication with a very high mortality rate. Herein, we propose a combined antioxidant–antibiotic therapy based on poly­(ε-caprolactone)-block-poly­(glutamic acid) polymer vesicle to treat infected diabetic wounds. This was realized by in situ decoration of stable, well-dispersed ceria nanoparticles onto ciprofloxacin (CIP)-loaded polymer vesicles. These resulting CIP-loaded and ceria-decorated polymer vesicles (CIP-Ceria-PVs) exhibited high superoxide dismutase mimetic activity to inhibit superoxide free radicals (the inhibition rate reached ∼50% at an extremely low cerium concentration of 1.25 μg/mL). When the cerium content is in the range of 5–20 μg/mL, the CIP-Ceria-PVs showed the highest protective capability to normal L02 cells from damage of superoxide free radicals. In addition, the CIP-Ceria-PVs exhibited enhanced antibacterial activity (the dosage of CIP in CIP-Ceria-PVs was reduced by 25–50% compared to free CIP). In vivo treatment of infected diabetic wounds was performed on a diabetic mice model. The CIP-Ceria-PVs could effectively cure infected diabetic wounds within 14 days. Overall, a combined antioxidant–antibiotic therapy was proposed by introducing ceria nanoparticles and CIP into polymer vesicles for the treatment of infected diabetic wounds.

We report the synthesis of highly transparent poly(stearyl methacrylate)-poly(2,2,2-trifluoroethyl methacrylate) (PSMA–PTFEMA) diblock copolymer nanoparticles via polymerization-induced self-assembly (PISA) in nonpolar media at 70 °C. This was achieved by chain-extending a PSMA precursor block via reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of TFEMA in n-tetradecane. This n-alkane has the same refractive index as the PTFEMA core-forming block at 70 °C, which ensures high light transmittance when targeting 33 nm spherical nanoparticles. Such isorefractivity enables visible absorption spectra to be recorded with minimal light scattering even at 30% w/w solids. However, in situ monitoring of the trithiocarbonate RAFT end-groups during PISA requires selection of a weak n → π* band at 446 nm. Conversion of TFEMA into PTFEMA causes a contraction in the reaction solution volume, leading to an initial increase in absorbance that enables the kinetics of polymerization to be monitored via dilatometry. At ∼98% TFEMA conversion, this 446 nm band remains constant for 2 h at 70 °C, indicating surprisingly high RAFT chain-end fidelity (and hence pseudoliving character) under monomer-starved conditions. In situ 19F NMR spectroscopy studies provide evidence for (i) the onset of micellar nucleation, (ii) solvation of the nanoparticle cores by TFEMA monomer, and (iii) surface plasticization of the nanoparticle cores by n-tetradecane at 70 °C. Finally, the kinetics of RAFT chain-end removal can be conveniently monitored by in situ visible absorption spectroscopy: addition of excess initiator at 70 °C causes complete discoloration of the dispersion, with small-angle X-ray scattering studies confirming no change in nanoparticle morphology under these conditions.

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RAFT dispersion polymerization of a prototypical methacrylic monomer, methyl methacrylate (MMA), is performed in mineral oil using various poly(lauryl methacrylate) (PLMA) precursors prepared with a trithiocarbonate-based RAFT agent. GPC analysis indicated reasonably narrow molecular weight distributions (M w /M n ≤ 1.39) for all diblock copolymers, with 1 H NMR studies indicating high MMA conversions (≥95%) for all syntheses. An efficient one-pot synthesis protocol enabled high blocking efficiencies to be achieved when targeting higher PMMA DPs. However, the relatively high glass transition temperature (T g ) of the corresponding core-forming PMMA block unexpectedly constrains the evolution in copolymer morphology during polymerization-induced self-assembly (PISA). More specifically, well-defined PLMA 22 −PMMA x spheres (x = 19−39) and relatively short worms (x = 69−97) can be obtained at 90 °C when using a PLMA 22 precursor but targeting higher x values (x ≥ 108) invariably leads to colloidally unstable aggregates of spheres, rather than long worms or vesicles. Interestingly, similar constraints were observed when targeting higher solids, when using n-dodecane instead of mineral oil, or when employing an alternative steric stabilizer block. Raising the PISA synthesis temperature from 90 to 115 °C (i.e., from below to above the T g of the final PMMA block) does not alleviate this unexpected problem. Moreover, only spherical nanoparticles can be obtained at 115 °C when targeting PMMA DPs between 50 and 400 with the same PLMA 22 precursor. This suggests that nanoparticle formation may occur by a chain expulsion/insertion mechanism at this relatively high reaction temperature. PLMA 22 −PMMA x nanoparticles were characterized in terms of their particle size and morphology using dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). DLS and TEM studies of a 0.1% w/w dispersion of PLMA 22 −PMMA 69 short worms indicated an irreversible worm-to-sphere transition on heating from 20 to 150 °C. Oscillatory rheology and TEM studies indicated that this thermal transition was only partially reversible for a 20% w/w dispersion of PLMA 22 −PMMA 69 short worms.