Multifunctional Immunomodulating Polymer Conjugates for Targeting and Treating Glycocalyx Dysfunction in Inflammatory Conditions

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Inflammatory and immune-mediated diseases, such as the rejection of transplanted organs, diseases involving the heart or blood vessels (cardiovascular diseases), or autoimmune diseases (e.g. diabetes or multiple sclerosis) account for 3 out 5 deaths worldwide. The endothelium is central to controlling inflammation and immune-mediated diseases since it lines the vasculature and marks the first point of contact between blood and all organs. The surface of the endothelial cells is covered by the glycocalyx, literally meaning “sugar coat”, which is a mesh-like structure of proteins and sugar polymers, marking the interface between bloodstream and organ tissue. Thus, a healthy glycocalyx represents the protective front line against inflammatory and immune-mediated diseases whereas glycocalyx shedding was found to correlate with disease severity and mortality. Therefore, we aim to target and treat glycocalyx dysfunction by rapidly rebuilding it through a new cell surface engineering approach, which should enable organs to maintain or reestablish their function. To do so, we are planning to develop polymer conjugates containing both glycocalyx targeting and immunomodulating functionalities. The conjugates should be able to selectively bind and retain on the endothelial cell surface and they will present sugar moieties which resemble the natural glycocalyx layer. We anticipate realizing a novel approach with significant therapeutic potential to improve treatment for inflammatory conditions where glycocalyx dysfunction is contributing to the pathology.