Nanomaterial-based modulation of inflammatory and cytokine networks for precision therapy in inflammatory bowel disease.

Inflammatory bowel disease (IBD), including Crohn' s disease and ulcerative colitis, is characterized by chronic intestinal inflammation driven by complex interactions among immune cells, intestinal epithelial cells, and the gut microbiota. Although biologic therapies targeting TNF-α, IL-12/23, and IL-23 have substantially improved clinical outcomes, heterogeneous therapeutic responses, systemic exposure, immunogenicity, and treatment resistance remain important clinical challenges. Nanotechnology has emerged as a versatile approach for regulating inflammatory processes in IBD by improving therapeutic stability, intestinal localization, and controlled delivery of biologically active cargos. Importantly, nanomaterial-based interventions regulate inflammatory responses through distinct mechanisms. Some nanoplatforms enable direct cytokine targeting by delivering cytokine-neutralizing antibodies, receptor-targeting molecules, or nucleic acid therapeutics that regulate cytokine expression. In contrast, many nanomaterials exert therapeutic effects through indirect cytokine network modulation by regulating oxidative stress, macrophage polarization, epithelial barrier dysfunction, inflammasome activation, or microbiota-associated immune responses. In this review, we summarize the role of inflammatory cytokine networks in IBD pathogenesis and discuss nanotechnology-enabled strategies for the delivery of cytokine-modulating biologics, including monoclonal antibodies, therapeutic proteins beyond antibodies, and nucleic acid therapeutics. We further examine representative nanoplatforms, including lipid-based nanoparticles, polymeric nanoparticles, biomimetic nanoparticles, inorganic nanoparticles, metal-based nanoparticles, and plant-derived nanoparticles, with emphasis on their mechanisms of action, formulation-specific advantages, and translational limitations. Furthermore, we critically evaluate different specific engineering considerations, including physicochemical properties, gastrointestinal stability, mucus interaction, and manufacturing scalability, to elucidate their impact on the translational potential of cytokine-modulating nanomedicines. Finally, we outline future directions for developing next-generation nanomedicines capable of achieving immune modulation in IBD.