Cerium-based nanoplatforms inhibiting goblet cell-associated antigen passages to stabilize barrier function in...

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by recurrent mucosal inflammation and ulceration. Since managing UC remains challenging due to frequent therapeutic resistance and relapse, there is a pressing need for new strategies that target the underlying disease mechanisms to achieve long-term remission. Recent studies have highlighted the functional heterogeneity of intestinal goblet cells (GCs) beyond their classical role in mucus secretion. The goblet cell-associated passages (GAPs) have been identified as a luminal antigen delivery to lamina propria immune cells. Excessive GAP opening contributes to barrier dysfunction and mucosal inflammation, suggesting that GAPs are a promising therapeutic target. In this study, we designed a chondroitin sulfate-coated cerium nanoplatform (CS/CeO₂) loaded with the BAPTA-AM (BA) to stabilize the barrier function in colon. Briefly, BA was used to suppress excessive GAPs opening during the early stage of colitis, thereby alleviating abnormal immune activation. At the same time, CeO₂ served as a carrier to restrict the free diffusion of BA. Meanwhile, CS enabled efficient targeting of ulcerative lesions, allowing CeO₂ to fully exert its reactive oxygen species (ROS)-scavenging and CT imaging capabilities. Upon oral administration, BA-CS/CeO₂ successfully inhibited aberrant GAPs opening in DSS-induced colitis mice and enhanced intestinal barrier integrity, with restoration of mucus layer thickness and epithelial tight junctions, alongside reduced immune cell infiltration. Overall, this work leverages GC heterogeneity to re-establish intestinal barrier homeostasis, offering a promising nanotherapeutic strategy for UC through GAPs regulation, ROS scavenging, and CT monitoring.