Macrophage-targeted emodin nanomaterials for effective acute pancreatitis treatment via modulation of the JNK pathway

CD44-targeted macrophage activation. The HEZ exhibited higher macrophage uptake efficiency in the inflammatory microenvironment, restored the mitochondrial membrane potential, alleviated oxidative stress, and effectively reduced the levels of cytokines in the AP cell model. Moreover, the formulation exhibited targeted enrichment and retention in the pancreas under AP conditions, blocking the systemic inflammatory amplification cascade, reducing approximately 50% of pathological damage in both pancreatic and lung tissues, decreasing the proportion of apoptotic pancreatic cells, and increasing the 15-day survival rate of AP mice from 15% to around 50%. Mechanistically, the formulation restored impaired macrophage mitochondrial function to a healthy state by inhibiting the JNK pathway. In summary, the multifunctional HEZ provides an upstream therapeutic strategy by targeting macrophages in AP, offering a novel and effective approach to potentially enhance AP treatment in the future.