冷冻休克单核细胞递送反义寡核苷酸脂质体治疗特发性肺纤维化研究

Abstract

Connective tissue growth factor (CTGF) is a key driver in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This study presents a groundbreaking supramolecular cryo-shock bone marrow mononuclear cell system for targeted drug delivery in IPF. We incorporated antisense oligonucleotides (ASO) to inhibit CTGF and simultaneously encapsulated nintedanib using the ZMO-E5-NPs carrier for synergistic delivery. The cryo-shock treatment enhances cellular structural integrity and preserves receptor functionality, thereby extending cell viability. By modifying the E5 peptide and conjugating it with DSPE-PEG-MAL, we developed a composite carrier, ZMO-E5-NPs, which demonstrates efficient lung-targeting capability. This system enables rapid nanoparticle capture by fibroblasts through matrix metalloproteinase 2 (MMP2) recognition, ensuring precise delivery of both ASO and nintedanib. In a bleomycin-induced pulmonary fibrosis mouse model, ZMO-E5-NPs-ASO (nintedanib-containing group) significantly attenuated fibrosis progression, improved lung function, and exhibited excellent biocompatibility and safety, highlighting its potential as a novel therapeutic strategy for respiratory diseases.