A Lipopolysaccharide-Directed Piezoelectric Sonosensitizer for Addressing Deep Periodontal Pocket Infections

Complete removal of dental plaque biofilms and associated pathogens from deep periodontal pockets, coupled with subsequent inflammation resolution, constitutes a pivotal challenge in current periodontitis therapy. Here, a targeted bactericidal and gas-based anti-inflammatory strategy to regulate the periodontal microenvironment was established. The strategy aimed to eradicate deep-seated infections by modifying piezoelectric bimetallic Ti/Mn-MOFs nanosheets with phenylboronic acid (PBA) and l-arginine (l-arg). PBA mediated chemical targeting against periodontal pathogens via lipopolysaccharide (LPS) covalent coupling. Under ultrasound (US) conditions, the sonodynamic therapy (SDT) mediated by Ti/Mn-MOFs was employed to generate reactive oxygen species, thereby oxidizing l-arg and controllably releasing nitric oxide (NO). NO exhibits dual therapeutic functions: primarily through its bactericidal activity to disrupt biofilms and concomitantly via suppression of NLRP3 inflammasome activation to mitigate inflammatory responses. With its relatively long half-life and large diffusion radius, a synergistic effect characterized by a concentrated burst of bactericidal effect and sustained maintenance of anti-inflammatory concentration occurs under the regulation of the ultrasonic switch mechanism. Moreover, the 3d orbital electrons of Mn hybridized with the energy levels of the Ti-O framework, effectively narrowing the band gap of the Ti-MOFs and optimizing the SDT efficiency. This strategy offers an approach to break the vicious cycle of infection-inflammation in periodontitis.