Dual‐ROS Sensitive Moieties Conjugate Inhibits Curcumin Oxidative Degradation for Colitis Precise Therapy

Abstract Curcumin, a natural bioactive polyphenol with diverse molecular targets, is well known for its anti‐oxidation and anti‐inflammatory potential. However, curcumin exhibits low solubility (<1 µg mL⁻¹), poor tissue‐targeting ability, and rapid oxidative degradation, resulting in poor bioavailability and stability for inflammatory therapy. Here, poly(diselenide‐oxalate‐curcumin) nanoparticle (SeOC‐NP) with dual‐reactive oxygen species (ROS) sensitive chemical moieties (diselenide and peroxalate ester bonds) is fabricated by a one‐step synthetic strategy. The results confirmed that dual‐ROS sensitive chemical moieties endowed SeOC‐NP with the ability of targeted delivery of curcumin and significantly suppress oxidative degradation of curcumin for high‐efficiency inflammatory therapy. In detail, the degradation amount of curcumin for SeOC is about 4‐fold lower than that of free curcumin in an oxidative microenvironment. As a result, SeOC‐NP significantly enhanced the antioxidant activity and anti‐inflammatory efficacy of curcumin in vitro analysis by scavenging intracellular ROS and suppressing the secretion of nitric oxide and pro‐inflammatory cytokines. In mouse colitis models, orally administered SeOC‐NP can remarkably alleviate the symptoms of IBD and maintain the homeostasis of gut microbiota. This work provided a simple and effective strategy to fabricate ROS‐responsive micellar and enhance the oxidation stability of medicine for precise therapeutic inflammation.