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

Small. 2024 May;20(20):e2306909. doi: 10.1002/smll.202306909. Epub 2023 Dec 15.

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.

Keywords: Helicobacter pylori; PDT; PTT; mucus penetration; targeted delivery.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Glycolipids / chemistry
  • Glycolipids / pharmacology
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori* / drug effects
  • Mice
  • Mucus* / metabolism
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Phototherapy / methods

Substances

  • rhamnolipid