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

Abstract

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.