Time‐Resolved Small‐Angle X‐Ray Studies of Spherical Micelle Formation and Growth During Polymerization‐Induced Self‐Assembly in Polar Solvents

Self-assembled poly(2-dimethylaminoethyl methacrylate)-poly(2-(diisopropylamino)ethyl methacrylate) (PDMA-PDPA) diblock copolymer nanoparticles are widely employed in biological applications, driving the need for a robust and scalable production method. Although polymerization-induced self-assembly (PISA) enables efficient nanoparticle synthesis at high solids content, its research and application to PDMA-PDPA are limited, likely due to kinetic trapping. Leveraging our recently developed generic time-resolved small-angle X-ray scattering (TR-SAXS) approach for PISA in non-polar media, a reversible addition-fragmentation chain transfer-mediated PDMA-PDPA PISA process in polar solvent that produces spherical micelles is examined. This study indicates that nano-scale monomer droplets might persist during the initial PISA stages. Extension of PDPA chains from partial PDMA macromolecular chain transfer agents drove complete self-assembly into solvated spherical cores, with TR-SAXS confirming the absence of any residual monomer within the spherical micelle core. Moreover, the evolution of phase behavior encompassed particle fusion and nascent PDMA-PDPA copolymer formation, followed by a kinetic power-law relationship. TR-SAXS measurements and modeling delivered compelling evidence clarifying the mechanisms underlying spherical micelle formation and growth during PISA in polar solvents.