Orally Delivered Nanotherapeutics with miRNA-497 Supplying for Inflammatory Bowel Disease.

The excessive generation of reactive oxygen species (ROS) contributes to the inflammatory process in inflammatory bowel disease (IBD), and ROS-scavenging therapy, which can promote tissue repair, has emerged as a promising therapeutic strategy for managing IBD and other inflammatory diseases. Although ROS-scavenging therapy holds significant therapeutic potential for the management of IBD, systemic off-target effects remain a major limitation. Recent studies have identified microRNA-497 (miR-497) as a promising therapeutic target for IBD as it can polarize proinflammatory M1 macrophages to a tissue-repair phenotype, promoting the clearance of ROS and potentially alleviating the symptoms of IBD. Despite its therapeutic potential, the poor stability and limited cellular uptake of miR-497 pose significant barriers to its clinical use. To address these limitations, a delivery strategy based on manganese-doped metal-organic framework (Mn-MOF) nanoparticles labeled with miR-497 (Mn-MOF@miR-497) was developed to effectively inhibit the production of proinflammatory cytokines and restore immunological tolerance in enterocytes disrupted by proinflammatory stimuli. The topical administration of Mn-MOF@miR-497 exhibited significant therapeutic efficacy in a murine model of IBD induced by dextran sulfate sodium (DSS) without any observable toxicity. This innovative nanotherapeutic strategy demonstrates remarkable potential as a targeted treatment approach for IBD, holding promise for exploring innovative therapeutic regimens for IBD management.