Self-driven Janus nanomotors empowering gastric mucus and biofilm penetration to potentiate antibiotic eradication of Helicobacter pylori

Helicobacter pylori ( H. pylori ) infection is a major etiological factor in diverse gastric pathologies, accounting for approximately 75 % of gastric cancer cases. Current clinical antibiotic therapy faces significant challenges due to drug resistance, gastric acid degradation, and the formidable barriers of gastric mucus and biofilm matrix. To tackle these challenges, antibiotic-loaded nanomotors were developed for self-propelled penetration through gastric mucus and biofilm matrix to achieve H. pylori eradication. Specifically, Janus-structured J-Ca/Si@PDA-CLR nanoparticles (NPs) were fabricated by sequentially depositing mesoporous silica layers onto CaO 2 NPs and asymmetrically coating them with clarithromycin (CLR)-loaded polydopamine (PDA). CaO 2 reacted with gastric acid and produced O 2 , combined with the intrinsic Janus coating, generates an asymmetrical protrusion force, enabling effective mucus penetration and preventing premature gastric emptying. The protection of mesoporous silica layers ensures long-term motion, more rapid and complete penetration across mucus layers, and deep infiltration into biofilms, enhancing drug retention in the stomach and targeted accumulation within biofilms. Following intragastrical administration in H. pylori -infected mice, the nanomotors exhibited efficient infiltration into submucosal tissues and deep distribution throughout the stomach wall, in stark contrast to their static counterparts confined to the gastric surface. Treatment with the nanomotors resulted in an 8000-fold reduction in gastric bacterial burden compared to static carriers. Remarkably, nanomotors given at half the CLR dose produced a 75-fold higher bactericidal effect compared to free CLR at twice the dose. Thus, this work establishes a feasible therapeutic strategy utilizing self-propelled NPs to overcome mucus barriers and achieve deep biofilm clearance, demonstrating significant potential for applications in treating biofilm-associated infections.