NIR-Activated ICG-Loaded M2 Macrophage Exosomes Ameliorate Periodontitis via Targeting Infection Inflammation and Oxidative Stress

Periodontitis is a chronic bacterial inflammatory disease. M2 macrophage-derived exosomes (M2-exos) possess targeted immunomodulatory abilities, but their role in mitigating oxidative stress (key for periodontitis treatment) remains unclear. In this study, we engineered M2-exos loaded with indocyanine green (ICG) (ICG@M2-exos) for the treatment of periodontitis. The constructed ICG@M2-exos effectively facilitated macrophage reprogramming from the M1 to the M2 phenotype, thereby resolving chronic inflammation and enhancing periodontal tissue repair. Under near-infrared irradiation, ICG conferred potent antibacterial efficacy against Porphyromonas gingivalis ( P. gingivalis ). Simultaneously, the exosomes released from ICG@M2-exos mitigated oxidative stress and decreased the expression of proinflammatory factors in THP-1 cells through promoting M2 polarization. In a rat model of P. gingivalis -induced periodontitis, the sustained release of ICG@M2-exos markedly expedited periodontal bone regeneration, accompanied by elevated levels of anti-inflammatory cytokines. Collectively, ICG-engineered M2-exos represent a promising strategy for tackling inflammatory periodontal conditions. This study demonstrates the dual advantages of ICG@M2-exos in near-infrared-responsive antibacterial activity and immunomodulation that work synergistically, laying a solid foundation for future clinical applications.