Nanotherapeutics for microenvironment modulation and immune homeostasis in periodontitis treatment

Periodontitis is a prevalent chronic inflammatory disease characterized by progressive destruction of tooth-supporting tissues, which may cause tooth loss and is closely linked to various systemic diseases. Recent insights into the immunopathogenesis of periodontitis highlight the potential of immunomodulatory strategies to restore periodontal homeostasis, thereby promoting tissue repair and regeneration. However, the poor bioavailability of current immunotherapies and the complexity of the periodontal microenvironment significantly constrain their clinical application. Nano-biomaterials offer promising therapeutic avenues for periodontitis treatment with their unique physicochemical properties and functional versatility. Moreover, they can integrate with other functional components to enhance targeted delivery, enable controlled release, and directly modulate the biological behavior of effector cells within the immune microenvironment, thus achieving synergistic antibacterial, immunoregulatory, and regenerative effects. This review outlines the pathogenesis of periodontitis and highlights recent advances in nanotherapeutics, with focus on designed strategies, multifunctional applications and underlying regulatory mechanisms. In addition, the challenges and limitations associated with clinical translation of nanotherapeutics are discussed to provide future directions for effective and safe periodontitis treatment.