ical reports demonstrated that severe periodontal disease is the sixth most prevalent disease, with a totaled prevalence of 11.2% and ≈743 million people affected worldwide, [2] accounting a major portion of the 442 billion USD year −1 cost for oral diseases. [3] Considering the pathogenesis of periodontitis, the exposure of periodontal tissues to the microorganisms would induce a defense response triggered by the host innate immune system, giving rise to the release of pro-inflammatory cytokines, thereby resulting in the damage of soft and hard tissues around the teeth.Current standard-of-care therapy aims at eliminating pathogenic microorganism and reducing the recolonization of bacteria by mechanical debridement. However, it is only partially effective for the majority of patients with periodontal disease, as the presence of bacterial was only regarded as the initiating factor. Once the host immune defense starts, it is hard to control the biological response to microbial challenge that can ultimately inflict damage upon the periodontal tissues. Therefore, it is highly desirable to develop host-modulation therapies for the treatment of periodontal disease. Macrophages represent the first line of host immune defense against periodontal pathogen infection both during the onset and resolution of inflammation. Macrophages can be classified into two groups based on the type of activation: pro-inflammatory M1 phenotype and anti-inflammatory M2 Macrophage polarization toward M1 phenotype (pro-inflammation) is closely associated with the destructive phase of periodontal inflammation. Nanoceria is verified to inhibit M1 polarization of macrophages by the favorable ability of reactive oxygen species (ROS) scavenging. However, the function of nanoceria on macrophage polarization toward M2 phenotype (anti-inflammation) in reparative phase of periodontal inflammation is quite limited. In this work, by introducing an antioxidant drug quercetin onto nano-octahedral ceria, synergistic and intense regulation of host immunity against periodontal disease is realized. Such nanocomposite can control the phenotypic switch of macrophages by not only inhibition of M1 polarization for suppressing the damage in the destructive phase but also promotion of M2 polarization for regenerating the surrounding tissues in reparative phase of periodontal disease. As-prepared nanocomposite can effectively increase the M2/M1 ratio of macrophage polarization in inflammatory cellular models by lipopolysaccharide stimulation. More importantly, the nanocomposite also exerts an improved therapeutic potential against local inflammation by significant downregulation of pro-inflammatory cytokines and upregulation of antiinflammatory cytokines in an animal model with periodontal inflammation. Therefore, this newly developed nanomedicine is efficient in ROS scavenging and driving pro-inflammatory macrophages to the anti-inflammatory phenotype to eliminate inflammation, thereby providing a promising candidate for treating periodontal inflammation.The ORCID i...

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Nowadays the multifunctional approaches to kill oral bacteria based on various nanocomposites have made great progress against periodontal infections, while the material structure and its functional integration are still insufficient. Herein, this work proposes a therapeutic strategy of chemodynamical therapy (CDT) and photothermal therapy (PTT) in monocrystals to effectively enhance the synergistic treatment. The CuS/MnS@MnO 2 consisting of hexagonal CuS/MnS nano-twin-crystal with a shell layer of MnO 2 is developed. In this nanosystem, the purpose of synergistic treatment of periodontitis by combining PTT/CDT is achieved within a CuS/MnS monocrystal, where CuS serves to achieve photothermal conversion, dissipate the biofilm and transfer the heat in situ to the integrated MnS, thus promoting the Mn 2+ -mediated CDT process. Meanwhile, the CDT process can generate the highly toxic hydroxyl radical to destroy extracellular DNA by utilization of endogenous H 2 O 2 produced by Streptococci in the oral biofilm, cooperating with PTT to dissipate the bacterial biofilm. With the design of the outer shell of MnO 2 , the selective bacteria-killing can be realized by producing oxygen which can protect the periodontal non-pathogenic aerobic bacteria and threaten the survival of anaerobic pathogens. Therefore, such design via multipattern strategies to combat microorganisms would provide a bright prospect for the clinical treatment of bacterial infections.