肺纤维化(PF)是一种可怕的肺部疾病,可导致肺通气功能障碍和呼吸衰竭。严重影响患者的身心健康。现有药物只能部分控制病情,容易产生毒副作用。抗炎治疗是缓解PF的重要步骤。雷公藤红素(CLT)具有显著的抗炎作用,可逆转巨噬细胞的M1型转化。在这项研究中,我们开发了载有CLT的脂质体,用叶酸(FA)修饰,指定的FA-CLT-嘴唇,通过靶向巨噬细胞促进药物递送。显示FA-CLT-Lips在体外更容易被巨噬细胞吸收,并促进M1巨噬细胞转变为M2巨噬细胞。此外,FA-CLT-Lips可以抑制Smad2/3的磷酸化,有效减少细胞外基质(ECM)的沉积和炎症因子的产生。这表明FA-CLT-Lips可以通过降低炎症来改善早期肺纤维化。体内研究表明,FA-CLT-Lips在肺组织中积累,以更好地减轻肺损伤和胶原蛋白沉积,与游离CLT相比毒性较小。总之,负载有CLT的FA受体靶向脂质体提供了安全可靠的PF治疗。
Pulmonary fibrosis (PF) is a horrible lung disease that causes pulmonary ventilation dysfunction and respiratory failure, severely impacting sufferers\' physical and mental health. Existing drugs can only partially control the condition and are prone to toxic side effects. Anti-inflammatory treatment is the committed step to alleviate PF. Celastrol (CLT) has significant anti-inflammatory effects and can reverse M1-type transformation of macrophages. In this study, we have developed liposomes loaded with CLT, modified with folate (FA), designated FA-CLT-Lips, which facilitate drug delivery by targeting macrophages. FA-CLT-Lips were shown to be more readily absorbed by macrophages in vitro and to encourage the transition of M1 macrophages into M2 macrophages. In addition, FA-CLT-Lips can inhibit the phosphorylation of Smad2/3, effectively reducing the deposition of extracellular matrix (ECM) and the production of inflammatory factors. This showed that FA-CLT-Lips can ameliorate early lung fibrosis by lowering inflammation. In vivo studies have shown that FA-CLT-Lips accumulate in lung tissue to better attenuate lung injury and collagen deposition, with less toxicity compared to free CLT. In summary, FA receptor-targeting liposomes loaded with CLT provide a secure and reliable PF therapy.