Dual delivery of agmatine and microRNA-126b using agmatine-mediated DNA nanotube assemblies for acute lung injury therapy

Acute lung injury (ALI) is characterized by widespread inflammation and oxidative stress , leading to impaired gas exchange and significant morbidity. In this study, we propose a potential approach using a magnesium-free DNA self-assembly strategy to assemble a DNA nanotube that carries agmatine and microRNA-126b mimics (NT AGM -126). Agmatine not only reduces electrostatic repulsion between DNA helices , thereby facilitating the folding of the DNA nanotube, but also serves as a drug that inhibits iNOS signaling. The microRNA-126b mimics restore the downregulated microRNA-126b in macrophages and suppress inflammation by targeting high mobility group box 1 (HMGB1). Preliminary results indicated that agmatine can effectively facilitate the assembly of the DNA nanotube, improve serum stability, and enhance the cellular uptake efficiency of NT AGM -126. Further in vitro and in vivo results demonstrate that NT AGM -126 effectively reduces oxidative stress and inflammation by downregulating iNOS and HMGB1, providing a combined therapeutic effect in ALI. This study highlights the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform for treating inflammatory diseases , broadening the application of DNA nanotechnology in biomedical research. This study introduces a promising therapeutic approach using a magnesium-free DNA self-assembly strategy to create a DNA nanotube (NT AGM -126) that carries agmatine and microRNA-126b mimics. The agmatine not only aids in the assembly and stability of the DNA nanotube but also inhibits iNOS signaling, while the microRNA-126b mimics restore downregulated microRNA-126b in macrophages and suppress inflammation by targeting HMGB1. Preliminary and further results demonstrate that NT AGM -126 effectively reduces oxidative stress and inflammation, providing a combined therapeutic effect in ALI. This study underscores the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform, broadening the application of DNA nanotechnology in the treatment of inflammatory diseases and advancing biomedical research.