Advances in Tetrahedral Framework Nucleic Acids (tFNAs) for Lung Injury Repair: Mechanisms, Therapeutic Applications, and Future Directions.

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.