Abstract
Inflammatory disorders are characterized by immune-mediated inflammatory cascades that can affect multiple organs. Cell-free DNA (cfDNA) is not only a biomarker for various inflammatory diseases, but also a driver in innate immune responses, offering emerging diagnostic and therapeutic possibilities for inflammatory diseases. This review begins by examining immune signatures in inflammation, with particular focus on the vicious cycle between cfDNA and inflammatory responses. We then discuss cfDNA detection strategies and their clinical applications as disease biomarkers. Crucially, we highlight design principles and formulation strategies for cfDNA-based interventions for inflammation regulation, considering physical, biochemical, and immunological properties of cfDNA. These approaches encompass advanced nanotechnologies such as drug loading, targeted delivery, inflammation-responsive release, and microenvironment reprogramming. Subsequently, we examine cfDNA intervention strategies for precision treatment of inflammatory diseases, including inflammatory bowel diseases, rheumatoid arthritis, sepsis, periodontitis, and psoriasis. Finally, we present key insights and future perspectives, as well as discuss translational challenges and clinical considerations, thereby paving the way for innovative approaches to inflammation modulation and disease management.