Engineered targeted Ce-based MOF nanozymes for ROS scavenging and inflammatory Reprogramming in chronic pancreatitis

Chronic pancreatitis (CP) is a lifelong progressive fibrotic inflammatory disorder for which no effective cure is currently available. Persistent and recurrent inflammatory stimulation induced by reactive oxygen species (ROS) is a key driver of pancreatic fibrogenesis, making oxidative stress a promising therapeutic target to halt disease progression. In this study, we developed a nanosystem, HC@CeMOF, consisting of a small-sized cerium-based metal-organic framework (CeMOF) core loaded with curcumin and coated with hyaluronic acid (HA), enabling precise targeting of inflamed pancreatic tissue. HC@CeMOF exhibits a small-sized particle size along with favorable cellular and biological safety profiles. Once administered in vivo, the nanosystem exploits the specific binding affinity of HA to CD44 receptors on macrophages to selectively accumulate at inflamed pancreatic sites. Subsequently, the cerium-based nanozyme efficiently scavenges ROS through the reversible redox cycling between Ce³⁺ and Ce⁴⁺, while the slow release of curcumin further suppresses the NF-κB signaling pathway and modulates inflammatory cytokine levels, thereby achieving synergistic anti-inflammatory and antioxidant effects. Collectively, these mechanisms substantially attenuate CP progression. This targeted ROS-scavenging and anti-inflammatory strategy holds promise as an alternative therapeutic approach for chronic pancreatitis.