Tetrahedral\nFramework Nucleic Acids Delivery of Pirfenidone\nfor Anti-Inflammatory and Antioxidative Effects to Treat Idiopathic\nPulmonary Fibrosis

Idiopathic\npulmonary fibrosis (IPF) is a chronic and irreversible\nlung disease, and developing an effective treatment remains a challenge.\nThe limited therapeutic options are primarily delivered by the oral\nroute, among which pirfenidone (PFD) improves pulmonary dysfunction\nand patient quality of life. However, its high dose and severe side\neffects (dyspepsia and systemic photosensitivity) limit its clinical\nvalue. Intratracheal aerosolization is an excellent alternative method\nfor treating lung diseases because it increases the concentration\nof the drug needed to reach the focal site. Tetrahedral framework\nnucleic acid (tFNA) is a drug delivery system with exceptional delivery\ncapabilities. Therefore, we synthesized a PFD-tFNA (Pt) complex using\ntFNA as the delivery vehicle and achieved quantitative nebulized drug\ndelivery to the lungs <i>via</i> micronebulizer for lung\nfibrosis treatment. <i>In vivo</i>, Pt exhibited excellent\nimmunomodulatory capacity and antioxidant effects. Furthermore, Pt\nreduced mortality, gradually restored body weight and improved lung\ntissue structure. Similarly, Pt also exhibited superior fibrosis inhibition\nin an <i>in vitro</i> fibrosis model, as shown by the suppression\nof excessive fibroblast activation and epithelial-mesenchymal transition\n(EMT) in epithelial cells exposed to TGF-β1. Conclusively, Pt,\na complex with tFNA as a transport system, could enrich the therapeutic\nregimen for IPF <i>via</i> intratracheal aerosolization\ninhalation.