From Spheres to Worms to Vesicles: Kinetic Control of Nanostructure Formation from the Same Block Copolymer

Abstract

Block copolymer self-assembly in solution offers a versatile platform for designing nanostructures with tailored morphologies in aqueous environments. While morphology is commonly controlled by adjusting block ratios, kinetic trapping of nanostructures represents a powerful yet underexplored strategy to direct shape and structure formation, for example in biomedical applications. In this study, we investigate the self-assembly behavior of the amphiphilic block copolymer poly[(butyl acrylate)50-co-(pyridyl disulfide ethyl acrylate)5]-block-(poly ethylene oxide)125-N3 (P(BA50-PDSA5)-b-PEO125-N3) using a solvent switch method. The polymer features a neutral, biocompatible hydrophilic block and a hydrophobic block with a low glass transition temperature (Tg). By systematically varying the initial solvent composition (DMSO/acetone), polymer concentration (1, 4, 7 mg/mL), and water addition rate (1, 2, 4, 20 mL/h), we demonstrate precise control over nanoparticle morphology. DMSO content above 80% favored vesicle formation, while balanced DMSO/acetone mixtures stabilized worm-like micelles. Lower polymer concentration of 1 mg/mL resulted in a decrease in the formation of non-spherical morphologies, and faster water addition rate of 4 mL/h broadened the worm phase, indicating a strong influence of kinetics on the final morphology. Characterization via asymmetric flow field-flow fractionation (AF4), dynamic light scattering (DLS), and cryogenic transmission electron microscopy (cryo-TEM) revealed sharp transitions and mixed phases, highlighting the sensitivity of the system to subtle assembly conditions. These findings provide mechanistic insights into morphology control and underscore the potential of kinetically guided self-assembly for designing shape-specific nanostructures, which is particularly relevant for biomedical applications where nanoparticle shape influences biodistribution, cellular uptake, and therapeutic efficacy.