Cerium Dioxide-based Nanotherapeutics For The Treatment Of Ulcerative Colitis

Ulcerative colitis（UC）is a chronic inflammatory disease of the intestine characterized by recurrent flare-ups and lacking a cure.Current treatments relay on anti-inflammatory drugs or immunosuppressants to alleviate acute symptoms.However,the long-term use of these agents could result in serious side effects,making it imperative to find new treatments for UC.In this study,we developed a drug-free nanotherapeutic based on cerium dioxide（Ce O₂）,which was formulated into both oral and enema forms.Our cellular and animal experiments demonstrated that this nanotherapeutic had excellent biological safety and was effective in alleviating UC by eliminating reactive oxygen species（ROS）and damage-associated molecular patterns（DAMPs）in the intestine,regulating the secretion of inflammatory factor and macrophage polarization,remodeling intestinal mucosal structure,and regulating intestinal flora.This innovative approach offers a promising new therapeutic strategy for treating clinical UC.The main research contents and results are as follows:Methods:1.Ce O₂ nanoparticles were synthesized,and then wrapped by Zeolitic imidazolate framework-8（ZIF-8）to form Ce O₂@ZIF-8 NPs with core-shell structure.2.The NPs were characterized by scanning electron microscopy,transmission electron microscopy,X-ray diffraction,X-ray electron spectroscopy,zeta potential,etc.3.Evaluate the scavenging capacity of Ce O₂@ZIF-8 NPs to ROS and DAMPs in vitro4.Evaluation of the cytocompatibility of Ce O₂@ZIF-8 NPs and it’s effect on macrophage polarization at the cellular level.5.Ce O₂@ZIF-8 NPs were prepared into oral and enema preparations,and their effect on improving ulcerative colitis was evaluated on the mouse model of acute ulcerative colitis.Results:1.Based on the rare earth material Ce O₂,a Ce O₂@ZIF-8 NPs with a core-shell structure were synthesized.2.In vitro experiments have demonstrated that Ce O₂@ZIF-8 NPs exhibit excellent ROS and DAMPs clearance effect.3.Subsequent cell experiments proved that Ce O₂@ZIF-8 NPs had good cytocompatibility.It can promote M2 polarization of macrophages,inhibit the expression of pro-inflammatory cytokines,and promote the expression of anti-inflammatory cytokines.4.In vivo animal experiments have suggested that both oral and enema preparations could effectively alleviate ulcerative colitis in mice by regulating macrophage polarization,reducing inflammatory response,regulating intestinal flora,and restoring colonic integrity.