Efficient active hydrogen delivery for drug-free radiation enteritis therapy in mice
Xianggui Yin, Changfen Bi, Yuanfang Chen, Xueyin Hu, Guangyou Shi, Shuqin Li, Wen Zhang, Longbo Ma, Saijun Fan, Luntao Liu
Abstract
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