Synergistic Amino and Hydroxyl Groups That Enhance SOD-Like Activity in Curcumin Carbon Dots for Improved Colitis Treatment
Yan Du, Xuehui Duan, Hanxiao Liu, Zhongjie Tang, Xu Li, Tianying Ren, Xinlei Chu, Y.‐M. Wang, Yunsai Wang, Wei Xu, Hongliang Wang, Yingyi Wang, Yingyi Wang, Yixuan Tang
Abstract
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 Lachnospiraceae, and normalizing key commensals such as Lachnospiraceae_NK4A136_group . 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.