The Rise of cfDNA-Scavenging Nanomaterials for Inflammatory Disease Therapy

Abstract

Cell-free DNA (cfDNA), released from damaged cells, acts as a critical danger-associated molecular pattern and plays a key role as a molecular trigger in various inflammatory diseases. Conventional anti-inflammatory therapies target downstream effectors, often causing systemic immunosuppression and facing long-term efficacy and safety limits. Recent advances in cfDNA-scavenging nanomaterials offer a novel therapeutic strategy by efficiently scavenging-cfDNA released from various sources that contribute to inflammation. We systematically review the burgeoning advances in cfDNA-scavenging nanomaterials, which represent a novel platform for modulating inflammation, and detail the mechanisms of these engineered cfDNA nanoscavengers to restore immune homeostasis, including competitive binding, electrostatic adsorption and enzymatic degradation. Crucially, we discuss the challenges impeding clinical translation, such as mitigating material toxicity, preventing binding saturation and cfDNA re-release, and enhancing in-vivo targeting specificity. Finally, we outline future perspectives for developing intelligent, multifunctional, and biocompatible nanomaterial platforms, emphasizing their potential for integration into precision immunotherapy against inflammatory diseases.