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Published on: August 10, 2018
Dual delivery of agmatine and microRNA-126b using agmatine-mediated DNA nanotube assemblies for acute lung injury
Chunfa Chen1, Quan Li2, Beinuo Wang3
1Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China; Chongqing Key Laboratory of Precision Medicine and Prevention of Major Respiratory Diseases, Chongqing 400037, China; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
Abstract:
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 (NTAGM-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 NTAGM-126. Further in vitro and in vivo results demonstrate that NTAGM-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. STATEMENT OF SIGNIFICANCE: This study introduces a promising therapeutic approach using a magnesium-free DNA self-assembly strategy to create a DNA nanotube (NTAGM-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 NTAGM-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.

