Overcoming antibiotic resistance caused by genetic mutations of Helicobacter pylori with mucin adhesive polymer-based therapeutics

• Published in: Biomaterials Vol. 308; p. 122541
• Main Authors: Lim, Byoungjun, Kim, Kyoung Sub, Ahn, Ji Yong, Na, Kun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2024
• Subjects: Adhesives - chemistry; Adhesives - pharmacology; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial photodynamic therapy; Antibiotics resistance; Drug Resistance, Bacterial - drug effects; Drug Resistance, Bacterial - genetics; Helicobacter Infections - drug therapy; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - drug effects; Helicobacter pylori - genetics; Humans; Mice; Mucin adhesive polymer; Mucins - chemistry; Mucins - metabolism; Mutation; Photochemotherapy - methods; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Polymers - chemistry; Mucin adhesive polymer; Antibacterial photodynamic therapy; Helicobacter pylori; Antibiotics resistance
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2024.122541

Herein, we describe the 3′-sialyllactose-polyethyleneimine-chlorine e6 conjugate (3PC), meticulously engineered to effectively target Helicobacter bacteria (H. pylori) within the gastric environment. The composition of 3PC comprises polyethyleneimine, a cationic polymer, 3′-sialyllactose, which exhibits a specific binding affinity for H. pylori surface proteins, and a photosensitizer capable of generating oxygen radicals in response to specific wavelengths. The distinctive feature of 3PC lies in its capacity to enhance interaction with the anionic mucus layer facilitated by electrostatic forces. This interaction results in prolonged residence within the intestinal environment. The extended vacation in the intestinal milieu overcomes inherent limitations that have historically impeded conventional antibiotics from efficiently reaching and targeting H. pylori. 3PC can be harnessed as a potent tool for antibacterial photodynamic therapy, and its versatility extends to addressing the challenges posed by various antibiotic-resistant strains. The exceptional efficacy of 3PC in enhancing intestinal residence time and eradicating H. pylori has been robustly substantiated in animal models, particularly in mice. In summary, 3PC is a formidable agent capable of eradicating H. pylori, irrespective of its antibiotic resistance status, by efficiently penetrating and selectively targeting the mucus layer within the gastric environment.