Antibody-Phototherapy Selectively Targets Harmful Oral Bacteria to Treat Periodontitis
The bacterial species P. gingivalis is a cause of periodontitis, a common form of inflammatory gum disease that in addition to damaging gums, teeth, and bone in the mouth, also contributes to the development of inflammatory age-related conditions elsewhere in the body. Here researchers report on a novel approach to selectively removing P. gingivalis from the mouse, using a combination of a photosensitive dye conjugated to an antibody that binds to surface features on this species of bacteria. When irradiated with near infrared light, this kills the targeted cells. Treating a mouse model of periodontitis in this way successfully reduced inflammation and resolved the condition.
Traditionally, periodontitis was viewed as a simple infection; however, it is now recognized as a complex polymicrobial disease driven by synergistic interactions within the oral microbiota and a subsequent aberrant host immune response. Periodontitis is typically initiated by a shift from symbiotic to dysbiotic microbial communities. In this process, 'keystone pathogens' such as Porphyromonas gingivalis, even at low abundance, can remodel the surrounding commensal bacteria into a highly inflammatory state.
Recently, a new cancer-targeted therapy called near-infrared photoimmunotherapy (NIR-PIT), which combines antibody-dye conjugates and near-infrared light, has emerged. The cell death mechanism of NIR-PIT is unique. Specifically, when the conjugate is irradiated with near-infrared light in the presence of sufficient electron donors, the hydrophilic side chain (silanol) of the IR700 molecule dissociates through a photochemical ligand reaction, and the remaining structure, including the antibody, rapidly becomes hydrophobic and aggregates. At the same time, the antibodies bound to the surface antigens also aggregate on the tumor cell membrane. The aggregation reaction of IR700 causes physical stress on the antigen-antibody complex and selectively destroys the target cells
We recently developed NIR photoantimicrobial-targeted therapy (NIR-PAT2) to treat infectious diseases. For NIR-PAT2, as targeting molecules, we exploit immunoglobulin Y (IgY). NIR-PAT2 with IgY could be used for body surface and lumens, such as skin, hair, eye, digestive tract. The aim of this study was to develop a bacteria-targeted therapeutic modality using NIR-PAT2. While we acknowledge the inherent limitations of single-pathogen targeting in a complex polymicrobial disease, we hypothesized that selectively eliminating a keystone species would disrupt the synergistic drivers of dysbiosis. We define this approach as a precision-modulating therapy, designed to selectively ablate P. gingivalis while preserving the ecological integrity of the oral community. Here, we demonstrate that NIR-PAT2 successfully modulates oral dysbiosis, leading to the resolution of periodontitis and the restoration of a healthy-associated microbial profile in a murine model.