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.
Recommended Citation
Bridges, C., Fu, L., Wang, D., Sterling, J. D., Liang, S., Baker, S. M., Yeow, J., & Lord, M. S. (2026). Cationic Poly(glucosamine)-Based Polymers Bind to Glycans with Varying Affinity Facilitating Transport Across the Glycocalyx of Endothelial Cells. Biomacromolecules, 27(2), pp. 1736-1749. American Chemical Society.
The definitive version is available at https://doi.org/10.1021/acs.biomac.5c02490
Department(s)
Business and Information Technology
Second Department
Chemical and Biochemical Engineering
International Standard Serial Number (ISSN)
1526-4602
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2026 American Chemical Society, All rights reserved.
Publication Date
09 Feb 2026
PubMed ID
41486967
Included in
Biochemical and Biomolecular Engineering Commons, Health Information Technology Commons, Technology and Innovation Commons
