Self‐Propelled Janus Micromotors with Cascade Microenvironments‐Responsiveness for Hydrogen‐Actuated Whole‐Stage Symptomatic Therapy of Helicobacter Pylori ‐Associated Gastritis

Abstract Helicobacter pylori ( H. pylori )‐associated gastritis remains a major global health burden, yet current therapies are limited by low targeting efficiency, rising antibiotic resistance, and inadequate mucosal repair. Here, this study presents a dynamically microenvironment‐adaptive Mg‐Bi@PLGA‐EC micromotor (MBE‐motor) for achieving hydrogen‐actuated whole‐stage symptomatic therapy of H. pylori ‐associated gastritis. The MBE‐motor consists of a magnesium (Mg) core for gastric acid‐driven propulsion, a poly(lactic‐co‐glycolic acid) interlayer encapsulating bismuth nanoparticles (BiNPs), and a negatively charged enteric coating (EC) for selective adhesion to inflamed gastric mucosa. Upon exposure to gastric acid, the Mg core generates hydrogen gas (H 2 ) and Mg 2+ ions, enabling autonomous mucus penetration, localized pH modulation, and programmed BiNP release. The in situ H 2 exerts dual regulatory effects by enhancing BiNP‐mediated bactericidal activity through increased bacterial membrane permeability, while simultaneously reprogramming the inflammatory microenvironment via reducing oxidative stress and promoting M2 macrophage polarization. Concurrently, Mg 2+ release promotes epithelial proliferation, migration, and angiogenesis, thereby accelerating mucosal regeneration. Both in vitro and in vivo studies demonstrate the MBE‐motor's robust bacterial eradication (≈95.4% clearance), suppression of inflammation, restoration of mucosal integrity, and preservation of gut microbiota homeostasis. This multifunctional microrobotic platform exemplifies a cascade‐responsive biofuel‐driven strategy for precise and comprehensive management of H. pylori ‐associated gastric diseases.