Photothermal therapy with regulated Nrf2/NF-κB signaling pathway for treating bacteria-induced periodontitis

Periodontitis is an inflammatory disease initiated by bacterial infection, developed by excessive immune response, and aggravated by high level of reactive oxygen species (ROS). Hence, herein, a versatile metal-organic framework (MOF)-based nanoplatform is prepared using mesoporous Prussian blue (MPB) nanoparticles to load BA, denoted as MPB-BA. The established MPB-BA nanoplatform serves as a shelter and reservoir for vulnerable immunomodulatory drug BA, which possesses antioxidant, anti-inflammatory and anti-bacterial effects. Thus, MPB-BA can exert its antioxidant, anti-inflammatory functions through scavenging intracellular ROS to switch macrophages from M1 to M2 phenotype so as to relieve inflammation. The underlying molecular mechanism lies in the upregulation of phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2) to scavenge ROS and subsequently inhibit the nuclear factor kappa-B (NF-κB) signal pathway. Moreover, MPB-BA also exhibited efficient photothermal antibacterial activity against periodontal pathogens under near-infrared (NIR) light irradiation. In vivo RNA sequencing results revealed the high involvement of both antioxidant and anti-inflammatory pathways after MPB-BA application. Meanwhile, micro-CT and immunohistochemical staining of p-Nrf2 and p-P65 further confirmed the superior therapeutic effects of MPB-BA than minocycline hydrochloride. This work may provide an insight into the treatment of periodontitis by regulating Nrf2/NF-κB signaling pathway through photothermal bioplatform-assisted immunotherapy.