Nanozymes in IBD therapy: Rational design, catalytic mechanisms and targeted therapies delivery

Scheme 1 Schematic illustration of nanozyme-based strategies for IBD therapy, depicting administration routes as well as the comprehensive framework spanning from rational design and catalytic mechanisms to targeted delivery systems. • Machine learning algorithms and structural engineering strategies enable the rational design of high-performance metal and non-metal nanozymes. • Nanozymes alleviate inflammatory bowel disease by efficiently scavenging reactive oxygen species and modulating pathological immune responses. • Microenvironment-responsive nanocarriers and bio-hybrid systems achieve precise therapeutic accumulation within inflamed intestinal tissues. Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder driven by oxidative stress and pathological immune activation. Current clinical treatments frequently yield suboptimal therapeutic outcomes and are hampered by substantial off-target effects. In this context, nanozymes, which are nanomaterials possessing intrinsic enzyme-mimicking activities, have arisen as a promising therapeutic platform for the management of IBD. This review systematically explores the rational design of nanozymes, focusing on how machine learning-guided discovery and structural engineering advance both metal-based and non-metal-based systems. We further elucidate their therapeutic mechanisms in IBD, highlighting their dual capacity to scavenge reactive oxygen and nitrogen species while modulating pathological immune responses. Additionally, we examine advanced delivery platforms, including microenvironment-responsive nanocarriers and bio-hybrid systems, which enable precise targeting of inflamed intestinal tissues. Finally, the review concludes by critically assessing the current challenges in clinical translation and offering future perspectives to facilitate the transition of nanozymes from bench to bedside.