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Updated: Jan 7, 2026

Facile and Efficient Preparation of Tri-component Fluorescent Glycopolymers via RAFT-controlled Polymerization
Published on: June 19, 2015
Cationic Poly(glucosamine)-Based Polymers Bind to Glycans with Varying Affinity Facilitating Transport across the
Claire Bridges1, Lu Fu1, Dan Wang1
1School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
Abstract:
Natural polysaccharides, such as chitosan, offer promising avenues for drug delivery due to their cytocompatibility and ability to interact with cell surfaces. However, the endothelial glycocalyx, a glycan-rich extracellular matrix, presents a barrier that must be navigated for effective intracellular delivery. This study investigates how cationic poly(glucosamine)-based polymers, functionalized with guanidinium or ammonium groups, interact with key glycocalyx components including hyaluronan (HA) and heparan sulfate (HS). We demonstrate that these cationic polymers form tunable biomolecular condensates with glycans, with stronger binding observed for sulfated glycans, HS and heparin, than unsulfated HA. Derivatized chitosan polymers with varied cationic side chains exhibit differential binding affinities and cellular association, with guanidinium-containing polymers showing enhanced interaction with endothelial cells expressing a mature glycocalyx. Quartz crystal microbalance with dissipation monitoring revealed reversible binding profiles influenced by ionic strength, and competitive displacement assays using condensates confirmed preferential binding to heparin over HA. Enzymatic degradation of the glycocalyx reduced polymer-cell association, underscoring the role of the glycans in facilitating the cellular uptake of these polymers. These findings elucidate the mechanisms by which cationic polymers traverse the glycocalyx and highlight the potential of considering the glycocalyx in the design of polymer systems for targeted drug delivery applications.
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