摘要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.