Self-Assembly of Glucose Containing “Janus-Type” Linear Dendritic Block Copolymers for Biomedical Applications

The self-assembly of highly branched Janus dendrimers (JD) into Janus dendrimersomes (JDS) comprised of a hydrophilic/hydrophobic bilayer has shown promise for drug encapsulation and delivery. However, at higher concentrations and degrees of generation, the hydrophilic portions of traditional JDs have proved to be cytotoxic. To improve biocompatibility, JDs have been decorated with saccharide groups which assisted in the self-assembly of non-toxic Janus glyco-dendrimersomes (JGDS). It has been seen that, due to distinct peptide/polymer hydrogen bonding interactions, saccharide stereochemistry plays an important role in carbohydrate functions such as biological recognition, protein binding, and peptide aggregation pathways. This work explores using synthetic glycopolymers as the hydrophilic layer to amplify the structures’ hydrogen bonding ability, potentially enhancing the self-assembly of JGDS. The stereospecific arrangements of the pendant saccharide groups may be used for cell targeting, lectin specific binding in the body, and to mimic the biological glyco-clustering effect. Linear glycopolymers were synthesized through reversible addition fragmentation chain transfer (RAFT) at different target molecular weights and coupled to polylactic acid (PLA) branched dendrons. While maintaining a constant molecular weight of the hydrophobic dendron and altering the hydrophilic segment, a multitude of nanostructures may be seen. Coupled conjugates and nanostructures were characterized through nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM).