Abstract: Lung injury is a pathological condition caused by a range of direct or indirect factors that disrupt the alveolar-capillary barrier and damage the structure of the lung parenchyma, leading to impaired gas exchange and compromised respiratory function. Lung injury shows a high incidence worldwide and remains associated with high mortality, and safe, effective, and reliable therapeutic strategies for this condition are still lacking. Tetrahedral framework nucleic acids (tFNAs) represent a significant advancement in nucleic acid nanotechnology. As novel therapeutic agents and nanocarriers, tFNAs possess an intrinsic capacity to scavenge reactive oxygen species, thus mitigating oxidative stress. Additionally, their unique tetrahedral geometry facilitates endocytosis-mediated cellular uptake and confers them with excellent tissue permeability, enabling them to traverse the lung mucosal barrier. These properties collectively enhance cell–drug interactions. As a result, tFNAs show multidimensional therapeutic potential for the treatment of lung injuries and provide innovative strategies for managing complex pathological conditions. This review summarizes the recent advances in the application of tFNAs for lung injury repair, with a focus on their mechanisms of action, treatment strategies, and current challenges. The goal of this review is to promote breakthroughs in lung injury treatment. This infographic illustrates all aspects of tetrahedral framework nucleic acid (tFNA) in lung injury treatment. The upper left part, “Intelligent Design of tFNA”, covers responses to ROS, miRNA, pH, and enzymes, which trigger drug release. The upper right part, “Challenges Faced by tFNA”, lists objectives, biosafety, and high cost. The lower right part, “tFNA as Delivery Carrier”, highlights cantilever, sequence replacement, mosaic, and vertex. The lower left part, “tFNA as a Drug”, emphasizes anti-inflammatory effects on macrophages (M1 to M2), ROS neutralization, immune regulation of T cells, and tissue repair. At the bottom, the advantages of tFNA include biodegradability, programmability, cell uptake, and tissue permeability.An infographic on the design, challenges, advantages and applications of tFNAs in the treatment of lung injury. Keywords: self-assembled DNA nanomaterials, tetrahedral framework nucleic acid, lung injury, pulmonary fibrosis, drug delivery, targeted therapy
Song et al. (Mon,) studied this question.
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