Surface-Engineered Titanium Carbide MXenzyme Boosts ROS-Scavenging and Anti-Inflammation Activities for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is persistent or recurrent intestinal inflammation. The severity of IBD is highly associated with an imbalance between M1 and M2 macrophages. In this study, a novel strategy is designed to modulate macrophage polarization by reducing intracellular reactive oxygen species (ROS) levels and regulating mitochondrial function. A scavenging ROS nanozyme, titanium carbide (Ti3C2), is synthesized to self-assemble with mannose-modified trimethyl chitosan to form nanoparticles (TTCM). The synthesized TTCM exhibits an excellent biocompatibility. Additionally, it remains stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). In vitro experiments show that TTCM significantly reduced ROS levels, restored mitochondrial membrane potential, increased superoxide dismutase (SOD) activity, and suppressed the TLR4/NF-κB pathway, hence promoting the repolarization of pro-inflammatory M1 macrophages toward the anti-inflammatory M2 phenotype. In addition, we found that TTCM amplified antioxidant efficacy when compared with Ti3C2. These effects enhanced the intestinal barrier. In vivo experiments utilizing a dextran sulfate sodium (DSS)-induced acute colitis mouse model revealed the anti-inflammatory and intestinal-barrier-protective effects of TTCM, effectively mitigating IBD progression. Consequently, the findings suggest that the oral delivery of ROS-scavenging nanocarrier systems holds significant promise as a potential and effective therapeutic strategy for IBD treatment.