posted on 2024-04-10, 11:05authored byXiaoling Cao, Chenggong Yu, Shengnan Cheng, Yuhan Wang, Zhijun Zhang, Jie Huang
Alleviating the injury of type II alveolar epithelial
cells (AEC
2s) and inhibiting the activation and differentiation of fibroblasts
are significant for improving the therapeutic effect of idiopathic
pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles
(ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small
interfering RNA targeting transforming growth factor β1 (siTGF-β1) were developed for enhanced IPF therapy. ASNPs
showed high loading and intracellular delivery efficiency for AST
and siTGF-β1. After the injection of ASNPs
in an IPF mice model, the loaded AST largely scavenged reactive oxygen
species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby
ensuring the integrity of the alveolar epithelium. Meanwhile, siTGF-β1, delivered by ASNPs, significantly silenced
the expression of TGF-β1 in fibroblasts, inhibiting the differentiation
of fibroblasts into myofibroblasts as well as reducing the excessive
deposition of extracellular matrix (ECM). The combined use of the
two drugs exhibited an excellent synergistic antifibrotic effect and
was conducive to minimizing alveolar epithelial damage. This work
provides a codelivery strategy of AST and siTGF-β1, which shows great promise for the treatment of IPF by simultaneously
reducing alveolar epithelial damage and inhibiting fibroblast activation.