A ROS-responsive fluorescent probe detecting experimental colitis by functional polymeric nanoparticles

Current evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). TotalROX (λabs/λem = 425/525 nm) is a ratiometric probe with high detection sensitivity and a superior capacity to monitor total cellular oxidative capacity. Herein, we investigated the potential of combining totalROX with an oral nanoparticle delivery system to detect the degree of colitis. This detection system also featured pH-responsive Eudragit S100, hyaluronic acid with high affinity to the CD44 receptor, and chitosan, and demonstrated improved loading efficiency and stability. An experimental mouse model of experimental colitis was induced by dextran sodium sulfate do that we could investigate the ability of our nanoparticles to target the colon and determine the degree of inflammation. We also determined and validated the positive correlation between the fluorescence intensity of the detection product (Ox670, λabs/λem = 650/675 nm) and myeloperoxidase activity (R² = 0.97) and the histopathological score (R² = 0.98). TotalROX had significant ability to measure reactive oxygen species (ROS) produced by cells under inflammatory conditions, as confirmed by in vitro experiments with Caco-2 cells. Collectively, the data generated demonstrate that when loaded with totalROX, these functional nanoparticles are promising tools for cellular imaging after oral administration. This is the first description of a ROS-responsive fluorescent probe to evaluate the degree of colitis in experimental animal models and provides a promising approach for the diagnosis of inflammation in IBD with fluorescence-guided colonoscopy.