Polydopamine Dual-Modal Nanotherapy Synergizes Photothermal Antibacterial and Nanozyme Anti-Inflammatory Effects for Periodontitis Treatment.

Introduction: Given the limitations associated with clinical curettage in the treatment of periodontitis, there is a pressing need to enhance the complete removal of plaque from deep periodontal pockets and to facilitate the repair of periodontal tissues through appropriate medical interventions. Despite the significant advancements of various local drug delivery systems (LDDS) for the adjunctive treatment of periodontitis, their efficacy remains constrained by two intertwined challenges: inadequate antibiofilm capability and excessive reactive oxygen species (ROS)-mediated tissue damage. Methods: To simultaneously overcome these dual barriers, we synthesized polydopamine nanoparticles (PDA NPs) through a straightforward and efficient self-polymerization process of dopamine, followed by the synthesis of nanoparticles on the surface via reductive methods to create multifunctional nanoplatforms (PAg). Results: Notably, these PDA nanoparticles, which are based on comprehensive nanocomposites, function as photothermal agents that enhance the therapeutic efficacy against biofilms in vitro through antibacterial photothermal therapy (PTT) under near-infrared laser irradiation. Furthermore, owing to the enzyme-like activity of PDA nanozyme, the engineered nanocomposite is capable of effectively scavenging ROS in Raw267.4 cells and human periodontal ligament cells under oxidative stress conditions. The in vitro and in vivo analyses demonstrated that live/dead staining of the biofilm, along with Western blot assessments of inflammatory markers, substantially augmented the antibacterial and anti-inflammatory efficacy. The nano-platform-based PAg nanoparticles developed in our study not only markedly enhanced the antibacterial effect through combination therapy but also efficiently reduced cellular ROS via the enzyme-like activity of the nanozyme. Conclusion: This dual-modal nanotherapy delivers a coordinated attack on periodontitis pathogenesis, including direct physical elimination of biofilms coupled with ROS scavenging to mitigate collateral tissue damage, thereby addressing the limitations of current LDDS.