Mucus and Biofilm Penetrating Nanoplatform as an Ultrasound‐Induced Free Radical Initiator for Targeted Treatment of Helicobacter pylori Infection

Helicobacter pylori (H. pylori) infection is closely associated with the development of various gastric diseases. The effectiveness of current clinical antibiotic therapy is hampered by the rise of drug‐resistant strains and the formation of H. pylori biofilm. This paper reports a sonodynamic nanocomposite PtCu3‐PDA@AIPH@Fucoidan (PPAF), which consists of dopamine‐modified inorganic sonosensitizers PtCu3, alkyl radicals (R•) generator AIPH and fucoidan, can penetrate the mucus layer, target H. pylori, disrupt biofilms, and exhibit excellent bactericidal ability. In vitro experiments demonstrate that PPAF exhibits excellent acoustic kinetic properties, generating a significant amount of reactive oxygen species and oxygen‐independent R• for sterilization under ultrasound stimulation. Simultaneously, the produced N2 can enhance the cavitation effect, aiding PPAF nanoparticles in penetrating the gastric mucus layer and disrupting biofilm integrity. This disruption allows more PPAF nanoparticles to bind to biofilm bacteria, facilitating the eradication of H. pylori. In vivo experiments demonstrate that ultrasound‐stimulated PPAF exhibited significant antibacterial efficacy against H. pylori. Moreover, it effectively modulated the expression levels of inflammatory factors and maintained gastrointestinal microbiota stability when compared to the antibiotic treatment group. In summary, PPAF nanoparticles present a potential alternative to antibiotics, offering an effective and healthy option for treating H. pylori infection. A gastrointestinal microbe‐friendly composite nanoparticle (PtCu3‐PDA@AIPH@Fucoidan, PPAF) is fabricated that can penetrate the gastric mucosal layer and target Helicobacter pylori. Nitrogen can be generated under ultrasound stimulation, which enhances the ultrasound cavitation effect and destroys the bacterial biofilm. Alkyl radicals can also be generated to ensure antibacterial effects in the low oxygen environment where H. pylori colonizes.