Ultrasonic nanoengineering of biocompatible lignin-ergothioneine hybrids for targeted membrane disruption and sustained oral eradication of Helicobacter pylori

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects approximately 4.4 billion people globally. In this study, a novel method combining high-intensity ultrasonic solvent treatment and homogenization was employed to functionalize and nano-transform lignin nanoparticles (LigNPs) for grafting ergothioneine (EGT), a natural hydrophobic antioxidant, onto LigNPs (EGT@LigNPs) to target the H. pylori cell membrane. Acetone, with its strong hydrogen bonding capacity, was found to aggregate lignin of various molecular weights and increase the concentration of phenolic hydroxyl groups. Transmission electron microscopy (TEM), dynamic light scattering (DLS), UV–vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) revealed that LigNPs with a regular spherical shape and uniform size 86.5 ± 0.41 to 354.6 ± 3.44 nm could be produced by adjusting the water/solvent ratio and stirring rate during the antisolvent process. EGT@LigNPs demonstrated sustained drug release over 48 h and exhibited superior antioxidant and anti-H. pylori activities compared to unloaded LigNPs and pure EGT. Additionally, EGT@LigNPs showed excellent biocompatibility with normal a fibroblast cell line (L929), enhancing metabolic activity and intracellular protein release in H. pylori. Bioimaging studies using TEM, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM) indicated that EGT@LigNPs adhered to the bacterial surface and destabilized and disrupted the cell membranes. These findings suggest that EGT@LigNPs hold novel a non-toxic oral drug delivery system for treating gastric infections caused by H. pylori.