Curcumin-stabilized silver nanoparticles target the Helicobacter pylori-tumor interface in gastric cancer

Gastric cancer remains a major global health burden, ranking among the leading causes of cancer-related mortality worldwide. Chronic infection with Helicobacter pylori is a well-established etiological factor, promoting sustained gastric inflammation, epithelial transformation, and tumor progression through modulation of the gastric microenvironment. Therapeutic strategies that simultaneously target microbial virulence and tumor cell survival remain limited. In this study, we developed curcumin-stabilized silver nanoparticles (AgNPs) as a dual-functional nanoformulation designed to modulate the tumor-associated microbiome while exerting direct anti-cancer effects. The nanoparticles were chemically synthesized with a controlled diameter of 15 ± 2 nm, enabling enhanced surface reactivity and biological interaction. Antimicrobial evaluation revealed potent activity against H. pylori, with an IC₅₀ of 3.86 µg/mL. Furthermore, AgNPs significantly inhibited urease activity-a critical virulence determinant for gastric colonization-achieving 80.46 ± 1.15% inhibition at 160 µg/mL. Broad-spectrum antibacterial efficacy was also observed against other tested strains, indicating potential for reshaping the tumor microbiome. Cytotoxicity assessment in AGS human gastric adenocarcinoma cells demonstrated substantial anti-proliferative activity, with 73.99 ± 2.13% reduction in cell viability. The integration of curcumin, a bioactive polyphenol with established anti-inflammatory and anti-neoplastic properties, with silver nanoparticles provides a synergistic platform targeting both microbial and tumor components of gastric carcinogenesis. Collectively, these findings highlight AgNPs as a promising microbiome-directed nanotherapeutic strategy for gastric cancer management, warranting further mechanistic and translational investigation.