Corona Length as a Key Design Parameter in Glycosylated Polyplex Micelles

Glycosylated nanostructures provide a powerful platform for mimicking multivalent carbohydrate presentation at the cell surface and hold great potential for functional biomaterials. Here, we report a series of glycosylated block copolymers containing poly(glucosyl methacrylate) (PGlcMA) blocks, and either polyanionic or polycationic blocks, that were synthesized via RAFT polymerization and postpolymerization modification. These polymers were complexed in aqueous solutions to form glycosylated polyplex micelles, enabling a systematic investigation of how the corona length and ionic block architecture influence electrostatic self-assembly. Dynamic light scattering analyses revealed that the micelle size is primarily determined by the block-length ratio between the neutral PGlcMA corona and the ionic segment. When two oppositely charged block copolymers were paired, the micelle size exhibited a non-monotonic dependence on corona length, arising from the balance between steric repulsion and interpolymer complexation. However, replacing one block copolymer with a homopolymer produced larger micelles due to reduced steric repulsion within the coacervate core. These results establish molecular-level design principles for engineering glycosylated polyplex micelles with tunable dimensions and stable glycosylated coronas. The results show, that the size and stability of glycosylated polyplex micelles are governed by the combined effects of glycosylated corona length and corona number, which together balance corona-induced steric repulsion against electrostatic coacervate core growth, and provides a foundation for the rational development of glycosylated nanoparticles for targeted delivery. Interpolyelectrolyte complexation between polyanionic glycosylated block copolymer and complementary polycationic polymer forms glycosylated polyplex micelles, whose hydrodynamic diameters are dictated by the balance between the number of glycosylated coronas and the absolute length of the glycosylated block. • Well-defined glycosylated block copolymers with polyanionic or polycationic blocks. • Architecting glycosylated polyplex micelles via interpolyelectrolyte complexation. • The micellar size is controlled by the glycosylated corona number and block length.