Cationic Cyclodextrin Loaded Photosensitizer Ce6 for the Treatment of Periodontitis

Periodontitis is a bacterial infectious disease. Photodynamic therapy (PDT) offers high selectivity, drug-resistance-free treatment, and immune regulation. The second-generation porphyrin photosensitizer Ce6 excels in reactive oxygen species (ROS) production. However, periodontitis pathogens' negative charge limits Ce6's interaction with them. This study prepared a modified cationic cyclodextrin (sPAM) and encapsulated Ce6 in an aqueous medium to create a nano-photodynamic system (Ce6@sPAM), which was characterized. In vitro evaluations assessed Ce6@sPAM's photodynamic performance, safety, antibacterial properties, and effects on immunoregulation. TEM images revealed Ce6@sPAM's irregular spherical shape, with a size of 236 nm by DLS and a Zeta potential of +16.4 mV. Ce6@sPAM exhibits a notably brief light half-life of merely 13 min, facilitating its swift in vivo clearance. SOSG and DCFH-DA fluorescence experiments showed Ce6@sPAM had stronger ROS generation (p < 0.05) and better bacterial penetration (p > 0.05) than Ce6. Co-incubation with Ce6@sPAM reversed bacterial surface potential from negative to positive. Bio-safety tests confirmed its excellent biocompatibility. In antibacterial tests, sPAM showed antibacterial properties, and Ce6@sPAM had a stronger effect than Ce6 under light (p < 0.001). Ce6@sPAM also exhibited high macrophage killing rates (> 90%) without specificity (p > 0.05) and can induce M1 macrophages to M2 polarization. Ce6-loaded modified cyclodextrin nanoparticles hold great promise for synergistic PDT in periodontitis treatment, especially in early stages for optimal immunomodulation.