Macrophage-Derived Extracellular Vesicles-Coated Palladium Nanoformulations Modulate Inflammatory and Immune Homeostasis for Targeting Therapy of Ulcerative Colitis.
Jiahui ChengYiming ZhangLiang MaWenxian DuQiang ZhangRifeng GaoXinxin ZhaoYujie ChenLixian JiangXiaoyang LiBo LiYan ZhouPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
Ulcerative colitis (UC) is a chronic inflammatory bowel disease mainly involving the colon and rectum, which features recurrent mucosal inflammation. The excessive production of reactive oxygen species (ROS) is a trigger for pathological changes such as cell apoptosis and disordered immune microenvironments, which are crucial for the progression of UC and can be a promising therapeutic target. Nowadays, the development of targeted therapeutic strategies for UC is still in its infancy. Thus, developing effective therapies based on ROS scavenging and elucidating their molecular pathways are urgently needed. Herein, a biomimetic nanoformulation (Pd@M) with cubic palladium (Pd) as the core and macrophage-derived extracellular vesicles (MEVs) as the shell is synthesized for the treatment of UC. These Pd@M nanoformulations exhibit multienzyme-like activities for effective ROS scavenging, excellent targeting ability as well as good biocompatibility. It is verified that Pd@M can regulate the polarization state of macrophages by inhibiting glycolysis, and decrease neutrophil infiltration and recruitment. In this way, the colonic inflammatory and immune microenvironment is remodeled, and apoptosis is prevented, ultimately improving colonic mucosal barrier function and alleviating colitis in the mouse model. This finding provides a promising alternative option for the treatment of UC patients.
Keyphrases
- ulcerative colitis
- reactive oxygen species
- oxidative stress
- cell death
- dna damage
- mouse model
- end stage renal disease
- cancer therapy
- adipose tissue
- newly diagnosed
- ejection fraction
- signaling pathway
- chronic kidney disease
- stem cells
- cell proliferation
- peritoneal dialysis
- weight gain
- endoplasmic reticulum stress
- cell cycle arrest
- drug delivery
- body mass index
- physical activity
- single molecule
- combination therapy
- replacement therapy
- patient reported
- pi k akt
- drug induced