Efficient active hydrogen delivery for drug-free radiation enteritis therapy in mice

Radiation enteritis, affecting over 90% of pelvic/abdominal radiotherapy patients, is primarily caused by radiation-induced reactive oxygen and nitrogen species (RONS). Active hydrogens, with broad-spectrum RONS scavenging ability, show radioprotective potential but face delivery challenges due to the intestinal mucus barrier and short lifespan. Here, we show drinkable, self-thermophoretic sodium alginate/chitosan oligosaccharide-coated hydrogenated molybdenum oxide nanomachines (HxMoO3@SA@COSs) that exhibit near-infrared (NIR)-driven directional motility and sustained active hydrogen release. In a male mouse model of radiation enteritis, HxMoO3@SA@COSs overcome the mucus barrier, prolong intestinal retention, and deliver active hydrogen to injury sites, enabling precise enteritis therapy. Beyond RONS scavenging, the released hydrogen induces anti-inflammatory macrophage polarization, increases goblet cell abundance, and modulates gut microbiota, promoting intestinal repair. This hydrogen-based, drug-free strategy demonstrates superior efficacy in treating radiation enteritis. The authors develop drinkable nanomachines to deliver active hydrogen to intestinal injury sites in mice, enabling drug-free radiation enteritis therapy by scavenging reactive species, reducing inflammation, modulating gut microbiota, and improving survival