The treatment of ulcerative colitis is harassed by its intricate pathogenesis and the harsh gastrointestinal environment.Herein,oral microbiota-regulating and inflammation-targeted polymersome-hydrogels are developed ...The treatment of ulcerative colitis is harassed by its intricate pathogenesis and the harsh gastrointestinal environment.Herein,oral microbiota-regulating and inflammation-targeted polymersome-hydrogels are developed by incorporating gallic acid and tumor necrosis factorα-specific siRNA-encapsulated polymersomes(GA-siTNFα-PS)into self-healable and eatable hydrogels(SHE-Gel)formed from thiolated sodium alginate and dopaminemodified oxidized inulin(DA-OIn)for oral RNAi therapy of ulcerative colitis.SHE-Gel is stable in stomach,resides in the intestine,and degrades in the colon by colon-specific inulinase.DA-OIn endows SHE-Gel antioxidative stress and prebiotic activities that modulate the diversity of gut microbiota.GA-siTNFα-PS released in the colon can adhere to the inflamed sites,resulting in selective delivery of siTNFαto macrophages.GA eliminates ROS and further protects siTNFαfrom degradation.Remarkably,GA-siTNFα-PS/SHE-Gel not only effectively blocks the progression of inflammation but also maintains the homeostasis of gut microbiota in the ulcerative colitis model.GA-siTNFα-PS/SHE-Gel can further combine with anti-TNFαantibody,restoring the intestinal immune and gut microbiota homeostasis in an advanced model of colitis in mice.The polymersomehydrogels with effective suppression of intestinal inflammation and modulation of gut microbiota provide a versatile and powerful strategy for treatment of ulcerative colitis.展开更多
基金supported by research grants from the National Natural Science Foundation of China(NSFC52033006)the National Post-doctoral Researcher Program(GZC20241187).
文摘The treatment of ulcerative colitis is harassed by its intricate pathogenesis and the harsh gastrointestinal environment.Herein,oral microbiota-regulating and inflammation-targeted polymersome-hydrogels are developed by incorporating gallic acid and tumor necrosis factorα-specific siRNA-encapsulated polymersomes(GA-siTNFα-PS)into self-healable and eatable hydrogels(SHE-Gel)formed from thiolated sodium alginate and dopaminemodified oxidized inulin(DA-OIn)for oral RNAi therapy of ulcerative colitis.SHE-Gel is stable in stomach,resides in the intestine,and degrades in the colon by colon-specific inulinase.DA-OIn endows SHE-Gel antioxidative stress and prebiotic activities that modulate the diversity of gut microbiota.GA-siTNFα-PS released in the colon can adhere to the inflamed sites,resulting in selective delivery of siTNFαto macrophages.GA eliminates ROS and further protects siTNFαfrom degradation.Remarkably,GA-siTNFα-PS/SHE-Gel not only effectively blocks the progression of inflammation but also maintains the homeostasis of gut microbiota in the ulcerative colitis model.GA-siTNFα-PS/SHE-Gel can further combine with anti-TNFαantibody,restoring the intestinal immune and gut microbiota homeostasis in an advanced model of colitis in mice.The polymersomehydrogels with effective suppression of intestinal inflammation and modulation of gut microbiota provide a versatile and powerful strategy for treatment of ulcerative colitis.
