In situ small-angle X-ray scattering studies of sterically-stabilized diblock copolymer nanoparticles formed during polymerization-induced self-assembly in non-polar media

Reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) is utilized to prepare a series of poly(stearyl methacrylate)-poly(benzyl methacrylate) (PSMA-PBzMA) diblock copolymer nano-objects at 90 °C directly in mineral oil. Polymerization-induced self-assembly (PISA) occurs under these conditions, with the resulting nanoparticles exhibiting spherical, worm-like or vesicular morphologies when using a relatively short PSMA₁₃ macromolecular chain transfer agent (macro-CTA), as confirmed by transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) studies. Only kinetically-trapped spherical nanoparticles are obtained when using longer macro-CTAs (<i>e.g.</i> PSMA₁₈ or PSMA₃₁), with higher mean degrees of polymerization (DPs) for the PBzMA core-forming block simply producing progressively larger spheres. SAXS is used for the first time to monitor the various morphological transitions that occur <i>in situ</i> during the RAFT dispersion polymerization of BzMA when targeting either spheres or vesicles as the final copolymer morphology. This powerful characterization technique enables the evolution of particle diameter, mean aggregation number, number of copolymer chains per unit surface area (<i>S</i>_agg) and the distance between adjacent copolymer chains at the core-shell interface (<i>d</i>_int) to be monitored as a function of monomer conversion for kinetically-trapped spheres. Moreover, the gradual evolution of copolymer morphology during PISA is confirmed unequivocally, with approximate 'lifetimes' assigned to the intermediate pure sphere and worm morphologies when targeting PSMA₁₃-PBzMA₁₅₀ vesicles. Within vesicle phase space, the membrane thickness (<i>T</i>_m) increases monotonically with PBzMA DP. Furthermore, a combination of dynamic light scattering (DLS), TEM and <i>post mortem</i> SAXS studies indicate that the lumen volume is reduced while the overall vesicle dimensions remain essentially constant. Thus the constrained vesicles grow inwards, as recently reported for an aqueous PISA formulation. This suggests a universal vesicle growth mechanism for all PISA formulations.