biostudies-literatureHuang GNational Natural Science Foundation of ChinaNational Key Research and Development Program of China181https://www.ebi.ac.uk/biostudies/studies/S-EPMC12918629biostudies-literatureUnknown24(1)Antibiotics remain the recommended first-line therapy for eradicating Helicobacter pylori infection. However, the harsh gastric physicochemical environment severely limits drug bioavailability, contributing to treatment failure (~10%), gut dysbiosis, and the emergence of antimicrobial resistance. Inspired by H. pylori adhesins binding to gastric epithelial glycan, we developed a biomimetic nanocomposite drug delivery system (BSNG) composed of genetically engineered adhesin-functionalized silk fibroin nanoparticles (BS-NPs) embedded within a fluid silk fibroin hydrogel (FSF-Gel) for targeted anti-H. pylori therapy. BS-NPs exhibit H. pylori-like adhesion to gastric epithelial cells, enabling prolonged gastric retention of over 72 h. FSF-Gel provides conformal coverage of the gastric mucus laJournal of nanobiotechnologySilk-based biomimetic nanocomposite for precision eradication of Helicobacter pylori and gut microbiome preservation.PMC12918629321727982022YFD120160032030103Huang GZhao PXia QTian CLiu QWang FWang YHe QfalseSilk-based biomimetic nanocomposite for precision eradication of Helicobacter pylori and gut microbiome preservation.Antibiotics remain the recommended first-line therapy for eradicating Helicobacter pylori infection. However, the harsh gastric physicochemical environment severely limits drug bioavailability, contributing to treatment failure (~10%), gut dysbiosis, and the emergence of antimicrobial resistance. Inspired by H. pylori adhesins binding to gastric epithelial glycan, we developed a biomimetic nanocomposite drug delivery system (BSNG) composed of genetically engineered adhesin-functionalized silk fibroin nanoparticles (BS-NPs) embedded within a fluid silk fibroin hydrogel (FSF-Gel) for targeted anti-H. pylori therapy. BS-NPs exhibit H. pylori-like adhesion to gastric epithelial cells, enabling prolonged gastric retention of over 72 h. FSF-Gel provides conformal coverage of the gastric mucus la2026-01-01T00:00:00Z2026 Jan2026-07-16T10:06:33.231Z2026-07-09T10:48:57.81ZS-EPMC129186294158852210.1186/s12951-026-04050-9