Ultrasound-Activated Persistent Luminescence Imaging and Bacteria-Triggered Drug Release for Helicobacter pylori Infection Theranostics

Helicobacter pylori (H. pylori) is recognized as a pathogenic factor related to gastrointestinal diseases and gastric cancer. The theranostics of H. pylori infection is confronted with challenges from colonization on the epithelial cell layer and formation of bacterial biofilms, which prevent interactions with imaging probes and antimicrobial agents. Herein, theranostic nanoparticles (NPs) are developed with ultrasonication (US)-propelled motion and US-excited persistent luminescence for precise imaging and efficient eradication of H. pylori. Mechanoluminescent SrAl₂O₄:Eu²⁺ (SAOE) and persistently luminescent ZnGa₂O₄:Cr³⁺ (ZGC) nanodots (NDs) were in situ deposited on mesoporous silica NPs to prepare mSZ NPs. mSZ-Clr@ePDA NPs were fabricated through surface adsorption of clarithromycin (CLR) and then coating with enzyme-responsive polydopamine layers (ePDA). US-activated SAOE NDs generate emissions to excite ZGC NDs for persistent emission of near-infrared (NIR) afterglows, but they are quenched by the ePDA coatings. The disintegration of ePDA layers by bacterial phospholipase rapidly restores NIR emissions for imaging of H. pylori biofilms and simultaneously triggers the CLR release. US-driven motion promotes NP penetration and CLR delivery across mucus into biofilms, leading to full destruction of the biofilm matrix and embedded bacteria. In an H. pylori-infection model, mSZ-Clr@ePDA/US treatment enhances the retention of NPs in the stomach and penetration across mucus and accumulation on the epithelial layer, and the US-activated persistent emission provides a real-time diagnosis of H. pylori infection without autofluorescence. The US-propelled accumulation of mSZ-Clr@ePDA NPs and local release of CLR in biofilms significantly eliminate bacterial burdens in gastric tissues at a lower dose of antibiotics. Thus, this study offers a feasible strategy to activate persistent emission in deep tissues and provides a potential theranostic solution for non-invasive imaging and efficient removal of H. pylori infection.