Non-anticoagulant heparins: glycan-mediated immune modulation and therapeutic applications

Non-anticoagulant heparins (NAHs) are modified derivatives of heparin that retain many of the biological activities of the parent compound while exhibiting reduced or absent anticoagulant effects. These modifications have unlocked new therapeutic potentials in various diseases, including inflammatory disorders, cancer, sepsis, and viral infections. This review explores the chemical modifications of NAHs, their mechanisms of action, structure-activity relationships, and therapeutic applications. NAHs exert anti-inflammatory, anticancer, antiviral, and vascular protective effects by interacting with key proteins like heparanase, P-selectin, and HMGB1. Furthermore, their application in drug delivery systems, such as hydrogels and nanoparticles, enhances localized therapeutic efficacy. The promising results from preclinical and clinical studies position NAHs as a valuable class of drugs with diverse therapeutic applications, particularly in oncology, infectious diseases, and critical care.