Eradicating <i>Helicobacter pylori</i> and reversing precancerous intestinal metaplasia by gastric epithelial cells-localizable oral nanomedicines.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42569414.
- Also identified by DOI 10.1016/j.bioactmat.2026.07.030 and PMC identifier 13450024.
- Licence recorded as CC BY-NC-ND.
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Abstract
The ability to treat <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection and eliminate its associated gastric cancer risk is highly desirable but has proven to be extremely difficult. In this study, pilot proteomic screening of clinical gastric mucosal samples suggested a progressive decline in Sirtuin 1 abundance along the <i>H. pylori</i>-associated pathological cascade. Based on these findings, gastric epithelial cells-localizable oral nanomedicines (GLONs) are developed, whereby <i>H. pylori</i> eradication and reversal of precancerous intestinal metaplasia (IM) are simultaneously achieved via Sirtuin 1 restoration. GLONs are constructed by coating resveratrol, lactoferrin, and disulfide modified-fucoidan (DFu) co-assembled nanoparticles (RLF) with engineered mucin-overexpressing gastric epithelial cell membranes. The shell of GLONs resists gastric acid, enhances mucus penetration and epithelial cells uptake. After internalization, DFu undergoes oxidative destabilization in the H<sub>2</sub>O<sub>2</sub>-enriched infectious microenvironment induced by <i>H. pylori</i>, thereby triggering RLF core dissociation and subsequent component release. The resveratrol restored <i>H. pylori</i> infection-induced impairment of Sirtuin 1, thereby activating autophagy. Meanwhile, lactoferrin promoted antimicrobial peptide production and synergized with fucoidan-mediated enhancement of antigen presentation, ultimately enabling the clearance of both intracellular and extracellular <i>H. pylori</i>. In metaplastic gastric cells, Sirtuin 1 repairs damaged DNA, and inhibits malignant proliferation. In mouse models, under the tested 7-day regimen, GLONs produced greater reductions in gastric <i>H. pylori</i> burden and more pronounced improvements in IM-related phenotypes than the abbreviated triple-therapy. GLONs represent an innovative and highly efficient therapeutic platform for <i>H. pylori</i> infection and its complications.