5-Aminosalicylic Acid-Derived Carbon Dots Nanozyme for Ulcerative Colitis Treatment via Inhibiting NF-κB/AGE-RAGE Pathway and Modulating Arachidonic Acid Metabolism

The vicious cycle of “oxidation-inflammation” is one of the important pathogenic mechanisms of ulcerative colitis (UC). Herein, the clinical first-line anti-inflammatory drug 5-aminosalicylic acid (5-ASA) and ethylenediamine were utilized as the precursor to develop antioxidant carbon dots (CDs) nanozyme (5-ASA-CDs) via the Schiff base reaction under room temperature for UC therapy. 5-ASA-CDs possessed superoxide dismutase-like activity and effectively eliminated various oxygen and nitrogen-free radicals. The hydroxyl groups on the 5-ASA-CDs surface were crucial for the antioxidant enzyme activity, while the carboxyl groups and amino groups had a relatively minor impact on the catalytic process. The phenolic hydroxyl groups on the surface of 5-ASA promoted carbonization and condensation reactions for CDs formation by reducing the activation energy of dehydration. 5-ASA-CDs nanozyme showed excellent biocompatibility, partial mitochondrial localization, and markedly suppressed lipopolysaccharide induced reactive oxygen species and pro-inflammatory cytokine transcription in vitro. 5-ASA-CDs effectively accumulated in the inflamed colon tissues. Compared with the same dose of 5-ASA, 5-ASA-CDs showed better therapeutic effects in vivo by inhibiting the NF-κB/AGE-RAGE signaling pathway and modulating arachidonic acid metabolism. This study elucidated the synthesis and catalytic mechanism of 5-ASA-CDs and clarified the anti-inflammatory and antioxidant mechanism of 5-ASA-CDs in UC treatment.