H2S gas-actuated microrobots with clawed geometry for radiation enteritis protection by regulating neuro-immune axis

Abstract

Radiation enteritis represents a critical complication associated with pelvic or abdominal radiotherapy, yet clinically available drugs show limited efficacy and significant side effects. The excessive reactive oxygen species induced by radiation and dysregulated inflammatory cascades are pivotal in the progression of radiation enteritis. Herein, H 2 S gas-propelled DCSP microrobots featuring long-term intestinal retention, reactive oxygen species scavenging, and neuro-immune regulation characteristics are meticulously designed by combining claw-shaped microcarriers with cerium-based metal-organic frameworks and H 2 S gas donor diallyl trisulfide. The clawed geometry and motility of DCSP microrobots enable active oral delivery and enhanced intestinal retention. The loaded cerium-based metal-organic framework nanozymes function as ROS scavengers to eliminate radiation-induced oxidative stress. Notably, the controlled, sustained release of H 2 S gas significantly suppresses neutrophil and macrophage infiltration and promotes macrophage polarization through modulation of the neuro-immune axis, thereby alleviating radiation-induced inflammation. In a murine model of radiation enteritis, the engineered microrobots mitigate radiation-induced damage, reconstruct intestinal barrier function, and drive gut microbiota change, thus promoting intestinal repair. This microrobotic platform offers a promising radioprotective approach against radiation enteritis, which is associated with modulation of neuro-immune axis.