Protease-Loaded CuS Nanoparticles with Synergistic Photothermal/Dynamic Therapy against F. nucleatum-Induced Periodontitis

Periodontitis is a chronic inflammatory disease inducedby a plaquebiofilm, which can lead to the destruction of the periodontal supporttissue and even teeth loss. The common strategies of periodontitistreatment are to eliminate bacterial/biofilm-related inflammationand subsequently inhibit alveolar bone resorption, for which antibiotictherapy is the most traditional one. However, impenetrable polymericsubstances on bacterial biofilms make it difficult for traditionalantimicrobial agents to take effect. In this study, a novel nanoparticleprotease-loaded CuS NPs was developed, combining the advances of photodynamicand photothermal therapy from CuS and enzymatic degradation of thebiofilm by a protease. The photothermal activity and the reactiveoxygen generation capacity of the designed nanoparticles were verifiedby the experimental results, constituting the basis of antibacterialfunction. Next, the high antimicrobial activity of CuS@A NPs onFusobacterium nucleatumand its biofilm was demonstrated.The proper hemo/cytocompatibility of CuS-based NPs was demonstratedby in vitro assays. Last, effective treatment againstperiodontitis was achieved in a rat periodontitis model through thesignificant efficacy of inhibiting bone resorption and alleviatinginflammation. Thus, the developed CuS@A NPs prove a promising materialfor the management of periodontitis.

Automated summary

Periodontitis is a chronic inflammatory disease caused by a plaque biofilm that can lead to the destruction of periodontal support tissue and tooth loss. Traditional methods of periodontitis treatment, such as antibiotic therapy, are often ineffective due to the presence of impenetrable substances on bacterial biofilms. In this study, a novel nanoparticle, CuS NPs loaded with protease, was developed for the management of periodontitis. The results showed that the designed nanoparticles had strong antibacterial properties and were effective in inhibiting bone resorption and alleviating inflammation in a rat periodontitis model. Hence, the CuS@A NPs hold promise for the treatment of periodontitis.