Regulation of inflammatory macrophages by oral mineralized metal-organic framework nanoparticles for the synergistic treatment of ulcerative colitis and liver injury

Abstract

The exacerbation of liver injury has been identified as a severe complication of ulcerative colitis (UC), due to its ability to trigger a systemic inflammatory response. The aggravation of both ulcerative colitis and liver injury is primarily attributed to the presence of inflammatory macrophages, which exhibit elevated expression of tumor necrosis factor alpha (TNF-α). Considerable efforts are being devoted to the development of drugs capable of effectively inhibiting TNF-α expression in inflammatory macrophages, with the aim of mitigating the severity of this complex disease. Glutathione (GSH) suppressed inflammation by neutralizing reactive oxygen species (ROS) and mitigating cellular damage. In this study, we designed biomimetic mineralized metal–organic framework nanoparticles encapsulating siTNF-α and GSH (ZIF-8/siTNF-α/GSH@CaCO3, ZTGC) for the purpose of reprogramming inflammatory macrophages. In this study, we verified the co-occurrence of ulcerative colitis and liver injury. The calcium carbonate present in ZTGC provided protection against degradation in the gastrointestinal environment, facilitating effective and sustained release of siTNF-α in inflammatory macrophages. Oral administration of ZTGC mitigated ulcerative colitis, ameliorated liver injury, and diminished systemic inflammation in vivo. These findings suggest that mineralized metal–organic framework nanoparticles have the potential to serve as an effective oral administration for the synergistic treatment of inflammatory diseases. This innovative approach provides new insights into the “two in one” treatment of these complications.