Biodegradable organosilica-based targeted and redox-responsive delivery system of resveratrol for efficiently alleviating ulcerative colitis

Ulcerative colitis (UC) is characterized by a low redox potential in the colon. Targeting redox-responsive strategies are highly desirable due to the capacity of improving the treatment efficiency of drugs against UC. Resveratrol (Res), a natural ingredient, possesses prominent anti-inflammatory activity. However, the limited bioavailability and poor water-solubility severely hinder its clinical translation. Herein, we fabricate an oral delivery carrier of Res-encapsulated tetrasulfide-containing organosilica nanoparticles (DSMSNs), functionalized by targeting component chondroitin sulfate (CS). Benefiting from smart “switch” and targeted “guider”, CS shell enables high internalization and promotes selective accumulation in colon epithelial cells and macrophages through CD44-mediated pathway; meanwhile, glutathione (GSH) response-mediated rapid disassembly exhibits targeted Res release and efficient biodegradation, consequently achieving enhanced intracellular delivery of Res, improved Res-enabled treatment and recovered gut microbial diversity in the colitis model to mitigate colonic inflammation. These findings thus bring fresh insights into the potential of MONs in UC treatment as an oral delivery platform.