Nanomaterial-Based Strategies Targeting IL-1 Signalling in Inflammatory Bowel Disease: Therapeutic Applications and Mechanistic Insights.

Inflammatory Bowel Disease (IBD) is a group of gastrointestinal disorders characterized by chronic relapsing inflammation, primarily comprising Ulcerative Colitis and Crohn's Disease. Interleukin(IL) -1 (IL-1) family plays a central role in the immunoregulation of IBD, where its aberrant activation amplifies inflammatory responses through nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, leading to excessive release of pro-inflammatory cytokines, disruption of the epithelial barrier, and mucosal damage. Although biological agents targeting IL-1, such as Anakinra and the neutralizing antibody Canakinumab, have demonstrated anti-inflammatory effects in animal studies and certain clinical trials, challenges including low bioavailability, short half-life, and insufficient targeting specificity remain unresolved. In recent years, the emergence of nanomaterial technology has provided novel insights for the precise modulation of IL-1 signaling through two principal strategies. By loading IL-1 blockers or regulatory molecules into targeted and environmentally responsive nanoplatforms, it is possible to achieve site-specific drug delivery and sustained release at inflammatory loci, significantly reducing local inflammation and promoting mucosal repair. Specifically, we highlight advanced nanotechnology platforms-including lipid-based nanocarriers, polymeric nanosystems, inorganic nanomaterials, and bio-derived vesicles-that enable stimuli-responsive drug release, active mucosal targeting, and intrinsic immunomodulation to overcome biological barriers in the gut. Notably, certain active nanomaterials can directly eliminate reactive oxygen species (ROS) and block NLRP3 inflammasome activation to suppress IL-1 production. This review summarizes the role of the IL-1 family in the pathogenesis of IBD and advances in nanomaterial-based targeting strategies. Furthermore, by exploring Quality-by-Design (QbD) approaches and personalized nanocarriers, we aim to provide a new theoretical foundation and research direction for the evolution of IBD therapy toward stratified precision medicine.