Sacrificing Knight for Pawn‐Queen Promotion: Sonosensitive Nano‐Xanthiums Orchestrate NO to Retain H 2 O 2 for Antibiofilm Therapy

ABSTRACT Biofilm infections present escalating clinical challenges due to their intrinsic resistance to conventional treatments, underscoring the urgent need for innovative therapeutic strategies. Here, we show a pioneering approach that leverages sacrificial nitric oxide (NO) to enhance hydrogen peroxide (H 2 O 2 ) retention for antibiofilm therapy. H 2 O 2 has the ability to produce hydroxyl radicals (•OH), the most potent oxidants in nature, but it is often neutralized by H 2 O 2 scavengers before •OH formation. Our design utilizes ultrasound irradiation to release NO from the biofilm‐anchoring nano‐xanthiums (G‐B@NXs), which subsequently interact with biofilm‐associated H 2 O 2 scavengers, including catalase and glutathione, to suppress the decomposition ability toward H 2 O 2 . Additionally, glucose oxidase on the surface of G‐B@NXs supplements H 2 O 2 production, facilitates its conversion into •OH, and exhibits effective biofilm sterilization in different infection models. Our strategy not only shows the promise for advancing antibiofilm applications but also provides novel insights into the development of NO‐assisted biomaterials.