Oral nanoparticle therapy for inflammatory bowel disease by Paneth cell regulation and mucus layer remodeling

Abstract

Increased intestinal permeability, gut microecology dysbiosis, and the development of inflammatory bowel disease (IBD) are closely linked. Defective Paneth cell (PC) differentiation and disrupted goblet cell (GC) mucus exacerbate intestinal inflammation, driving IBD progression. In this context, we investigated the therapeutic effects of tungsten-encapsulated zinc nanoparticles (W@ZnNPs) in murine models of IBD. W@ZnNPs, with their high gastric stability and minimal side effects, have been found to enhance the mucosal barrier by improving Paneth and goblet cell functions, thus mitigating gut microbiota dysbiosis-induced inflammation. Orally delivered, W@ZnNPs outperformed mesalamine and other nanoadjuvants in ameliorating colitis, mainly through a dual mechanism of tungsten-mediated editing of Enterobacteriaceae and zinc-mediated modulation of intestinal cells. Most importantly, W@ZnNPs hold the potential to restore host-microbe interactions, making them a promising nanotherapeutic for IBD treatment.