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Realveolarization with inhalable mucus-penetrating lipid nanoparticles for the treatment of pulmonary fibrosis in mice

Sci Adv. 2024-07; 
Yan Wang , Jing Zhang , Ying Liu , Xiao Yue , Kun Han , Zhichao Kong , Yuanmin Dong , Zhenmei Yang , Zhipeng Fu , Chunwei Tang , Chongdeng Shi , Xiaotian Zhao , Maosen Han , Zhibin Wang , Yulin Zhang , Chen Chen , Anning Li , Peng Sun , Danqing Zhu , Kun Zhao , Xinyi Jiang
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摘要

The stemness loss-associated dysregeneration of impaired alveolar type 2 epithelial (AT2) cells abolishes the reversible therapy of idiopathic pulmonary fibrosis (IPF). We here report an inhalable mucus-penetrating lipid nanoparticle (LNP) for codelivering dual mRNAs, promoting realveolarization via restoring AT2 stemness for IPF treatment. Inhalable LNPs were first formulated with dipalmitoylphosphatidylcholine and our in-house-made ionizable lipids for high-efficiency pulmonary mucus penetration and codelivery of dual messenger RNAs (mRNAs), encoding cytochrome b5 reductase 3 and bone morphogenetic protein 4, respectively. After being inhaled in a bleomycin model, LNPs reverses the mitochondrial dysfunction t... More

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