Mucus‐Penetrating Nanoassembly as Potential Oral Phototherapeutic Formulation against Multi‐Drug Resistant Helicobacter pylori Infection

Abstract Helicobacter pylori ( H. pylori ) infection presents increasing challenges to antibiotic therapies in limited penetration through gastric mucus, multi‐drug resistance (MDR), biofilm formation, and intestinal microflora dysbiosis. To address these problems, herein, a mucus‐penetrating phototherapeutic nanomedicine (RLs@T780TG) against MDR H. pylori infection is engineered. The RLs@T780TG is assembled with a near‐infrared photosensitizer T780T‐Gu and an anionic component rhamnolipids (RLs) for deep mucus penetration and light‐induced anti‐ H. pylori performances. With optimized suitable size, hydrophilicity and weak negative surface, the RLs@T780TG can effectively penetrate through the gastric mucus layer and target the inflammatory site. Subsequently, under irradiation, the structure of RLs@T780TG is disrupted and facilitates the T780T‐Gu releasing to target the H. pylori surface and ablate multi‐drug resistant (MDR) H. pylori . In vivo, RLs@T780TG phototherapy exhibits impressive eradication against H. pylori . The gastric lesions are significantly alleviated and intestinal bacteria balance is less affected than antibiotic treatment. Summarily, this work provides a potential nanomedicine design to facilitate in vivo phototherapy in treatment of H. pylori infection.