Synergistic Amino and Hydroxyl Groups That Enhance SOD-Like Activity in Curcumin Carbon Dots for Improved Colitis Treatment

Inflammatory bowel disease (IBD) is a globally prevalent inflammatory disorder with limited therapeutic options due to efficacy-safety trade-offs. Herein, we rationally designed polyethylenimine (PEI)-functionalized curcumin-derived carbon dots (cu@CDs-po) as a multifunctional nanotherapeutic agent for colitis management. Combined experimental and computational analyses revealed that the synergistic interplay between surface-engineered amino and hydroxyl groups significantly enhanced the superoxide dismutase (SOD)-like activity of cu@CDs-po by 5.51-fold compared to unmodified cu@CDs, enabling efficient reactive oxygen species (ROS) scavenging and anti-inflammatory effects. PEI modification further improved cellular uptake and intestinal targeting. In a murine dextran sulfate sodium (DSS)-induced colitis model, cu@CDs-po effectively alleviated colon injury, restored intestinal barrier integrity, suppressed pro-inflammatory cytokines, and remodeled the immune microenvironment through T-cell suppression and M2 macrophage/Treg polarization. Critically, 16S rDNA sequencing revealed that cu@CDs-po induced targeted gut microbiota remodeling by restoring the Firmicutes/Bacteroidota ratio, suppressing pro-inflammatory Proteobacteria, enriching beneficial taxa such as <i>Lachnospiraceae</i>, and normalizing key commensals such as <i>Lachnospiraceae_NK4A136_group</i>. Functional analysis links these microbial shifts to enhanced metabolic and immune-related pathways. This study establishes a surface-chemistry-guided strategy for engineering catalytic carbon dots capable of simultaneously modulating oxidative stress, immune responses, and gut microbiota homeostasis, offering a promising and translatable paradigm for IBD nanomedicine.