Nanogel-coated nanozymes for ulcerative colitis targeted treatment by restoring redox homeostasis and anti-inflammatory activity

Excessive accumulation of reactive oxygen species (ROS) and overloaded immune system are key pathological features of ulcerative colitis (UC), but conventional treatments (such as aminosalicylates and immunosuppressants) often prove inadequate and have significant side effects. Here, an orally administrable PSGI utilized inulin (IN) as an outer shell and hollow mesoporous Prussian blue (HMPB) nanoparticles loaded with the aminosalicylate drug salazosulfapyridine (SASP) (PS) was developed to treat UC by scavenging ROS, reducing pro-inflammatory factors. After oral administration, IN can protect the drug-loaded nanoparticles from degradation by the enzymes of the upper gastrointestinal tract, easily penetrate into the lower gastrointestinal tract and reach the colon, where the IN shell could be degraded under the action of the colon-specific enzyme inulinase, to achieve the specific release of drugs that act like a "band-aid", adhering the inflamed colon through a combination of enzymatic degradation and electrostatic adsorption, thereby prolonging drug retention at the site of inflammation, providing an improved synergistic therapy for UC. PSGI demonstrated a significant preventive effect in the mouse dextran sodium sulfate (DSS)-induced colitis model, with no obvious damage to major organs. This is because the ROS clearance effect of prussian blue (PB) itself enhances and complements the anti-inflammatory effect of SASP, thereby reducing the dosage of SASP and lowering the risk of potential side effects. Overall, PSGI has demonstrated good anti-inflammatory activity and biosafety in both in vivo and in vitro studies. We hope that this oral targeted nanoplatform for the treatment of UC can address key challenges such as targeted drug delivery, improved efficacy, and reduced side effects in the treatment of colitis.