Zr-porphyrinic MOF PCN-224 enables sequential antibacterial and inflammation-modulating PDT for periodontitis

Periodontitis is a chronic inflammatory disease driven by microbial dysbiosis and a dysregulated host response, leading to soft-tissue destruction and alveolar bone loss. Antibacterial photodynamic therapy (aPDT) can rapidly suppress pathogens via light-triggered reactive oxygen species (ROS). Here, we report zirconium-based porphyrinic metal-organic framework (MOF) nanoparticles, PCN-224, as a bifunctional platform that couples early antibacterial aPDT with subsequent immunomodulation within the periodontal microenvironment. PCN-224 demonstrated excellent biocompatibility in vitro and in vivo. Under 660 nm irradiation, PCN-224 effectively generated singlet oxygen (¹O₂) and reduced Porphyromonas gingivalis burden. After uptake by RAW 264.7 macrophages, PCN-224 attenuated lipopolysaccharide-induced inflammation by lowering intracellular ROS levels, restoring superoxide dismutase activity, decreasing nitric oxide release, suppressing NF-κB signaling, accompanied by reduced IL-6, IL-1β, and iNOS and partial recovery of anti-inflammatory mediators. In a ligature-induced mouse model, local PCN-224 injection combined with 660 nm illumination decreased inflammatory infiltration and alleviated alveolar bone resorption. Collectively, PCN-224 provides a time-sequenced antibacterial-to-anti-inflammatory therapeutic effect and represents a potential MOF-enabled strategy for periodontitis management.