Abstract

Pathogenesis, progression, and therapeutic response of numerous digestive system tumors are associated with reduced intestinal barrier integrity. Here, we find that oral delivery of enterocyte-mimicking butyrate-loaded nanoparticles (EMBNs) capable of repairing the gut barrier can inhibit the occurrence, growth, and metastasis of digestive system tumors. EMBNs are prepared via loading butyrate into electrostatically complexed and sodium triphosphate-stabilized chitosan/hyaluronic acid nanoparticles, which are further coated with cell membranes extracted from enterocytes. The presented membrane receptors adsorb lipopolysaccharide and zonulin, known promoters of intestinal barrier impairment, while the loaded butyrate strengthens the function of the intestinal barrier. Mechanistically, the inhibition of autophagy in enterocytes and the promotion of a healthy microbial composition contribute to the repair of the gut barrier. Oral ingestion of EMBNs suppresses the disturbance of the liver immune microenvironment via alleviating the disruption of the intestinal barrier, achieving potent inhibition against hepatocellular carcinoma and hepatic metastasis of colonic carcinoma in dextran sulfate sodium-induced model in male mice. The reinforcement of the gut barrier spotlights a strategy to prevent and treat digestive system tumors.