Multifunctional DNA nanomaterials: a new frontier in rheumatoid arthritis diagnosis and treatment.

Rheumatoid arthritis (RA) remains a challenging autoimmune disease due to its complex and heterogeneous pathophysiology, which complicates therapeutic and diagnostic efforts. Advances in DNA nanotechnology have introduced DNA nanomaterials as promising tools to overcome these barriers. This review focuses on three primary categories of DNA nanomaterials applied in RA: DNA nanostructures, DNA aptamers, and DNA-modified nanoparticles. DNA nanostructures, such as tetrahedral framework nucleic acids (tFNAs) and DNA origami, demonstrate anti-inflammatory properties and facilitate precise, controlled drug delivery. DNA aptamers, functioning as molecular recognition ligands, surpass traditional antibodies with their high specificity, low immunogenicity, and thermal stability, offering significant potential in biomarker detection and therapeutic interventions. While DNA-modified nanoparticles, which integrate DNA with materials like gold or lipids, have shown significant progress in bioimaging and drug delivery in other fields, their application in RA remains limited and warrants further exploration. Furthermore, advancements in stimulus-responsive systems are being explored to enable controlled drug release, which could significantly improve the specificity and efficiency of DNA nanomaterials in therapeutic applications. Despite their immense potential, challenges such as stability under physiological conditions, safety concerns, and clinical regulatory complexities persist. Overcoming these limitations is essential. This review highlights how DNA nanomaterials, beyond serving as delivery platforms, are poised to redefine RA treatment and diagnosis, opening the door to more personalized and effective approaches.