Emerging nanomaterials for cfDNA clearance: A new frontier in inflammatory disease therapy.

Abstract

Cell-free DNA (cfDNA), a damage-associated molecular pattern, plays a pivotal role in initiating and perpetuating inflammatory responses in a wide range of diseases. Recent advances in nanotechnology have enabled the design of diverse nanomaterials that can bind or degrade cfDNA, offering promising therapeutic avenues. This review systematically summarizes cfDNA-targeting nanomaterials, including cationic polymers, metal-based constructs, and inorganic frameworks for efficient adsorption. Catalytic platforms such as deoxyribonuclease (DNase)-loaded nanocarriers and DNase-mimetic nanozymes are also highlighted for their potential in direct cfDNA degradation. Furthermore, we discuss combinatorial therapeutic strategies that integrate cfDNA clearance with anti-inflammatory therapy, immunomodulation, and reactive oxygen species scavenging to achieve synergistic inflammation control. The therapeutic relevance of these strategies is explored across multiple inflammatory disease models, including autoimmune diseases, infection-induced inflammation, acute injuries, and chronic inflammatory conditions. By bridging nanotechnology and immunopathology, cfDNA-targeted nanomedicine represents a powerful paradigm for precise and durable inflammatory resolution. Finally, we outline current challenges in clinical translation and discuss future directions for the rational design and optimization of cfDNA-scavenging nanotherapeutics.