Supramolecular Photothermal Cascade Nano-Reactor Enables Photothermal Effect, Cascade Reaction, and In Situ Hydrogelation for Biofilm-Associated Tooth-Extraction Wound Healing.

Due to the emergence of drug resistance in bacteria and biofilm protection, achieving a satisfactory therapeutic effect for bacteria-infected open wounds with conventional measures is problematic. Here, we construct a photothermal cascade nano-reactor (CPNC@GOx-Fe 2+ ) through a supramolecular strategy through hydrogen bonding and coordination interactions between chitosan-modified palladium nano-cube (CPNC), glucose oxidase (GOx), and ferrous iron (Fe 2+ ). CPNC@GOx-Fe 2+ exhibits excellent photothermal effect and powers the GOx-assisted cascade reaction to generate hydroxyl radicals, enabling photothermal and chemodynamic combination therapy against bacteria and biofilms. Further proteomics, metabolomics, and all-atom simulation results indicate that the damage of hydroxyl radical to the function and structure of the cell membrane and the thermal effect enhances the fluidity and inhomogeneity of the bacterial cell membrane, resulting in the synergistic anti-bacterial effect. In the biofilm-associated tooth extraction wound model, hydroxyl radical generated from the cascade reaction process could initiate the radical polymerization process to form a hydrogel in situ for wound protection. In vivo experiments confirm synergistic anti-bacterial and wound protection can accelerate the healing of infected tooth-extraction wounds without affecting the oral commensal microbiota. This study provides a way to propose a multifunctional supramolecular system for the treatment of open wound infection. This article is protected by copyright. All rights reserved.