Tetrahedral Framework Nucleic Acids Delivery of Pirfenidone for Anti-Inflammatory and Antioxidative Effects to Treat Idiopathic Pulmonary Fibrosis,ACS Nano

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Tetrahedral Framework Nucleic Acids Delivery of Pirfenidone for Anti-Inflammatory and Antioxidative Effects to Treat Idiopathic Pulmonary Fibrosis
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-14 , DOI: 10.1021/acsnano.4c06598
Yuting Xie ₁ , Sirong Shi _{2,

3} , Weitong Lv ₂ , Xinyu Wang ₁ , Lin Yue ₁ , Conghui Deng ₁ , Doudou Wang ₁ , Jing Han _{4,

5} , Tinghong Ye ₁ , Yunfeng Lin _{2,

3}

Affiliation

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease, and developing an effective treatment remains a challenge. The limited therapeutic options are primarily delivered by the oral route, among which pirfenidone (PFD) improves pulmonary dysfunction and patient quality of life. However, its high dose and severe side effects (dyspepsia and systemic photosensitivity) limit its clinical value. Intratracheal aerosolization is an excellent alternative method for treating lung diseases because it increases the concentration of the drug needed to reach the focal site. Tetrahedral framework nucleic acid (tFNA) is a drug delivery system with exceptional delivery capabilities. Therefore, we synthesized a PFD-tFNA (Pt) complex using tFNA as the delivery vehicle and achieved quantitative nebulized drug delivery to the lungs via micronebulizer for lung fibrosis treatment. In vivo, Pt exhibited excellent immunomodulatory capacity and antioxidant effects. Furthermore, Pt reduced mortality, gradually restored body weight and improved lung tissue structure. Similarly, Pt also exhibited superior fibrosis inhibition in an in vitro fibrosis model, as shown by the suppression of excessive fibroblast activation and epithelial-mesenchymal transition (EMT) in epithelial cells exposed to TGF-β1. Conclusively, Pt, a complex with tFNA as a transport system, could enrich the therapeutic regimen for IPF via intratracheal aerosolization inhalation.

中文翻译：

四面体框架核酸递送吡非尼酮具有抗炎和抗氧化作用，治疗特发性肺纤维化

特发性肺纤维化（IPF）是一种慢性且不可逆的肺部疾病，开发有效的治疗方法仍然是一项挑战。有限的治疗选择主要通过口服途径提供，其中吡非尼酮（PFD）可改善肺功能障碍和患者生活质量。然而，其高剂量和严重的副作用（消化不良和全身光敏性）限制了其临床价值。气管内气溶胶化是治疗肺部疾病的极好替代方法，因为它增加了到达局灶部位所需的药物浓度。四面体框架核酸（tFNA）是一种具有卓越递送能力的药物递送系统。因此，我们使用 tFNA 作为递送载体合成了 PFD-tFNA （Pt）复合物，并通过微量雾化器实现了定量雾化药物到肺部的给药，用于治疗肺纤维化。在体内，Pt 表现出优异的免疫调节能力和抗氧化作用。此外，Pt 降低了死亡率，逐渐恢复了体重并改善了肺组织结构。同样，Pt 在体外纤维化模型中也表现出优异的纤维化抑制，如暴露于 TGF-β 1 的上皮细胞中过度成纤维细胞活化和上皮-间质转化（EMT）的抑制所示。总之，Pt 是一种以 tFNA 作为运输系统的复合物，可以通过气管内雾化吸入丰富 IPF 的治疗方案。

更新日期：2024-09-14

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