Genetically Engineered CXCR4-modified Exosomes for Delivery of miR-126 mimics to Macrophages Alleviate Periodontitis

Biofilm related diseases are a group of diseases that tolerant antimicrobial chemotherapies therefore refractory. Periodontitis as a non-device chronic biofilm disease induced by dental plaque, can serve as an excellent in vivo model for studying the important implications of host factors in the biofilm microenvironment. Macrophage activity is one of the key factors that modulate the progression of inflammatory destruction in periodontitis, thus an important host immunomodulatory factor. In this study, the decrease of microRNA-126 (miR-126) with the recruitment of macrophages in periodontitis is confirmed in the clinical samples, and a strategy to target-deliver miR-126 to macrophages is explored.Exosomes overexpressing C-X-C motif chemokine receptor 4 (CXCR4) loaded with miR-126 (CXCR4-miR126-Exo) are successfully constructed, which reduce the off-target delivery to macrophages and regulate macrophages toward the anti-inflammatory phenotype. In vivo local injection ofCXCR4-miR126-Exo into sites of periodontitis in rats effectively reduces the bone resorption and osteoclastogenesis, and inhibited the progression of periodontitis. These results provide new insights for designing novel targeted delivery system of immunomodulatory factor to treat periodontitis and other biofilm related diseases.