Cholesterol Functionalized Nanoparticles Are Effective against <i>Helicobacter pylori</i> , the Gastric Bug: A Proof‐of‐Concept Study

Helicobacter pylori chronic infection is the highest risk factor for the development of gastric cancer, being this Gram-negative bacterium classified as carcinogenic. The mounting resistance of H. pylori to antibiotics calls for innovative therapeutic strategies. Here, the proof-of-concept studies that support the development of a "trojan horse" therapeutic strategy based on cholesterol-grafted nanoparticles (Chol-NP) to counteract H. pylori infection are depicted. The bacterium ability to specifically recognize and bind to surface grafted cholesterol is demonstrated by its adhesion to cholesterol(Chol)-functionalized self-assembled monolayers (SAMs) on gold substrates (2D Chol-SAMs) in a concentration dependent manner, with optimal Chol-SAMs prepared with 25% Chol-polyethylene glycol (PEG)-thiol in solution (75% tetra(ethylene glycol)-thiol). These results further show that cholesterol functionalized gold nanoparticles (3D Chol-SAMs, Chol-NP) eradicate H. pylori at a minimum bactericidal concentration of 125 µg mL^-1. Chol-NP kill H. pylori through internalization and membrane rupture, as observed by transmission electron microscopy (TEM). Chol-NP are cytocompatible (human gastric adenocarcinoma (AGS) cell line), non-hemolytic and innocuous to bacteria representative of the gut microbiota (Escherichia coli and Lactobacillus acidophilus). This study supports the further development of cholesterol functionalized biomaterials as an advanced and targeted treatment for H. pylori infection.