Architecting Well-Defined Glyco-Nanoparticles from pH- and Temperature-Responsive Glycosylated Triblock Terpolymers

Stimuli-responsive glycosylated nanoparticles hold great promise for mimicking complex biological glycans, yet current fabrication methods often lack versatility in tuning the morphology and responsiveness. Here, we report a solvent-selective self-assembly approach using multiresponsive glycosylated triblock tercopolymers designed with pH- and temperature-responsive segments. These polymers form well-defined nanoparticles, including spheres, cylinders, and worm-like aggregates, which can be modulated under external stimuli. Furthermore, we fabricated a diverse range of glycosylated nanoparticles by altering the sequence of the blocks within the terpolymers. Their well-defined morphologies were visualized via cryogenic transmission electron microscopy (cryo-TEM), and their size distributions were analyzed via dynamic light scattering (DLS). Our results demonstrate that integrating multiple stimuli-responsive elements in triblock terpolymers enables structural control of glycosylated nanoparticles. The morphological evolution of these nanoparticles corresponds to changes in the macromolecular configuration triggered by variations in the pH, temperature, and block sequence. This approach offers new opportunities for developing biomimetic materials for targeted delivery and glycan-based sensing.