Metal polyphenol network/cerium oxide artificial enzymes therapeutic nanoplatform for MRI/CT-aided intestinal inflammation management

Intestinal inflammation, such as ulcerative colitis (UC), is a condition in which there is chronic or recurring inflammation of the gastrointestinal tract. Designing safe, effective, and multifunctional nanomedicines is one of the current difficulties in the treatment of UC. Here we developed a delivery nanosystem based on metal polyphenol network/cerium oxide artificial enzymes (MPN@CeOx) to manage UC and evaluate the severity of inflammation by MRI/CT imaging. MPN@CeOx was engineered by Fe3+ and epigallocatechin gallate (EGCG) wrapped around CeOx. Increased levels of oxidative stress in the inflammatory lesion facilitated the release of Fe3+ and EGCG from MPN and liberated CeOx. EGCG with anti-oxidative and anti-inflammatory effects plus CeOx with superoxide dismutase (SOD)-like activity effectively scavenged reactive oxygen species (ROS) and reduced pro-inflammatory cytokines to protect cells from oxidative damage. In addition, H2O2-responsive releasing of Fe3+ at the site of inflammation and Ce elements in CeOx enable MRI/CT imaging of UC. In mice colitis models, oral administration of enteric-coated MPN@CeOx alleviated intestinal inflammation and intestinal barrier dysfunction. RNA sequencing analysis revealed that MPN@CeOx ameliorated UC symptoms mainly through inflammation-related signaling pathways. MPN@CeOx with multilevel inflammation management and multimodal imaging capabilities represents an innovative diagnosis and treatment approach for UC.