CaGA nanozymes inhibit oxidative stress and protect mitochondrial function in ulcerative colitis therapy

Ulcerative colitis (UC) is a long-term inflammatory bowel disease characterized by intense inflammation of the colorectal mucosa. Overproduction of reactive oxygen species exacerbates the progression of UC, which is linked to mitochondrial impairment and dysbiosis of the intestinal microbiota. CaGA nanozymes have demonstrated efficacy in the treatment of UC. The modulation of M1 and M2 polarization of macrophages by CaGA nanozymes has been demonstrated to be useful in reducing inflammation. Furthermore, CaGA nanozymes regulate the M1 and M2 polarization of macrophages, efficiently decreasing inflammation. The oral delivery of CaGA nanozymes resulted in their enrichment in inflamed areas of the colon and effectively reduced colonic damage in mice with DSS-induced colitis by improving the repair of the intestinal barrier. An investigation of 16S rDNA sequencing revealed that CaGA nanozymes regulate populations of both pathogenic and helpful bacteria and impact the progression of ulcerative colitis by influencing the tricarboxylic acid (TCA) cycle. Thus, CaGA nanozymes may be employed in the management of ulcerative colitis to control the intestinal milieu and improve the preservation of the intestinal barrier by decreasing the invasion of inflammatory cells and restoring mitochondrial activity.

Statement of significance

CaGA nanozymes exhibit multifunctional enzymatic activity, effectively eliminating cellular RONS with robust antioxidant capacity. CaGA nanoenzymes promote macrophage M1 to M2 polarization and produce anti-inflammatory effects. CaGA nanozymes increase cell viability by restoring impaired mitochondrial function, reducing reactive oxygen species (ROS) production, and restoring the ability of mitochondria to produce ATP. CaGA nanozymes modulate intestinal flora diversity and composition, potentially influencing inflammatory pathways via aromatic compound metabolism. They participate in cellular energy and biosynthesis, regulating ulcerative colitis (UC)-related intestinal function through the tricarboxylic acid (TCA) and urea cycles. Calcium ions bind to GA nanomedicine and small particles are readily absorbed by inflammatory cells, preventing diarrhea from being rapidly excreted.