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

ABSTRACT 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.