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 () and Luntao Liu ()
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Xianggui Yin: Chinese Academy of Medical Sciences & Peking Union Medical College
Changfen Bi: Chinese Academy of Medical Sciences & Peking Union Medical College
Yuanfang Chen: Chinese Academy of Medical Sciences & Peking Union Medical College
Xueyin Hu: Chinese Academy of Medical Sciences & Peking Union Medical College
Guangyou Shi: Chinese Academy of Medical Sciences & Peking Union Medical College
Shuqin Li: Chinese Academy of Medical Sciences & Peking Union Medical College
Wen Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Longbo Ma: Chinese Academy of Medical Sciences & Peking Union Medical College
Saijun Fan: Chinese Academy of Medical Sciences & Peking Union Medical College
Luntao Liu: Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-64270-9

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