Fe(III)-based deep eutectic solvent-modified nano barium titanate composite hydrogel for photothermal-sonodynamic synergistic treatment of periodontitis.

For the treatment of periodontitis, Fe(III)-based deep eutectic solvents (DESs) were designed and synthesized, which further served as photothermal conversion agents to modify barium titanate (BTO) for the first time. Notably, the DESs composed of protocatechuic acid, ethylene glycol, and FeCl3 (PGF) exhibited the strongest photothermal conversion capacity. PGF modification extended the light absorption range of BTO into the near-infrared region, achieving a photothermal conversion efficiency of 19.53%. This enhancement not only improved charge separation efficiency but also significantly boosted the generation of reactive oxygen species (ROSs). The BTO@PGF composite nanoparticles could respond to near-infrared light (NIR) and ultrasound (US) simultaneously, and their synergistic effects significantly enhanced the generation of multiple ROSs. To enable precise treatment of periodontitis for combined photothermal therapy (PTT) and sonodynamic therapy (SDT), the BTO@PGF nanocomposites were incorporated into the unique hydrogel composed of polyethyleneimine (PEI), polyacrylic acid (PAA), and fucoidan (FUC). This composite hydrogel could form hydrogel in situ in the humid oral environment, and the increased ROSsin photothermal-sonodynamic therapy (PTT-SDT) led to bacterial cell membrane destruction and leakage of nucleic acids and proteins, thereby exerting potent antibacterial effects. Antibacterial efficacy exceeding 90% was achieved against S. aureus, E. coli, and P. gingivalis, along with effective removal of biofilms. Additionally, the hydrogel demonstrated favorable anti-swelling property stability, and excellent biocompatibility. After treatment, the hydrogel could be easily removed through mechanical operation, minimizing potential side effects.