Multifaceted roles of heparin and its derivatives in inflammation and cancer: Mechanisms, clinical applications, and future directions.

Heparin and its derivatives have garnered increasing attention due to their multi-targeted anti-inflammatory and anti-cancer properties. This review systematically summarizes their molecular mechanisms and applications in inflammatory diseases and cancer. Structurally, heparin's highly negative charge and heterogeneity enable it to bind and regulate key molecules such as nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase 2, interleukin-6, and transforming growth factor-beta 1. These interactions inhibit pro-inflammatory signaling pathways, modulate the immune microenvironment, and disrupt pathways related to angiogenesis and tumor metastasis. Clinical evidence indicates significant improvements in the prognosis of patients with pneumonia, colitis, and pancreatitis, while preclinical studies reveal anti-cancer effects, including the inhibition of tumor cell proliferation and enhanced responses to immunotherapy. Furthermore, heparin-based nano-delivery systems offer promising strategies for expanding the therapeutic applications of heparin, particularly in targeted and synergistic anti-tumor therapies. However, the precise molecular mechanisms, individualized dosing regimens, and optimal combination therapies remain to be fully elucidated. Future research should prioritize the development of innovative targeted delivery systems, identification of multi-dimensional biomarkers, and integration of interdisciplinary therapeutic approaches to advance the translation of heparin and its derivatives into precision medicine for inflammation and cancer.