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

0301 basic medicine Pulmonary Fibrosis Lipids Idiopathic Pulmonary Fibrosis Pulmonary Alveoli Mice Mucus Bleomycin Disease Models, Animal 03 medical and health sciences Alveolar Epithelial Cells Administration, Inhalation Liposomes Animals Nanoparticles Humans Biomedicine and Life Sciences RNA, Messenger
DOI: 10.1126/sciadv.ado4791 Publication Date: 2024-06-12T17:58:25Z
ABSTRACT
The stemness loss-associated dysregeneration of impaired alveolar type 2 epithelial (AT2) cells abolishes the reversible therapy idiopathic pulmonary fibrosis (IPF). We here report an inhalable mucus-penetrating lipid nanoparticle (LNP) for codelivering dual mRNAs, promoting realveolarization via restoring AT2 IPF treatment. Inhalable LNPs were first formulated with dipalmitoylphosphatidylcholine and our in-house-made ionizable lipids high-efficiency mucus penetration codelivery messenger RNAs (mRNAs), encoding cytochrome b5 reductase 3 bone morphogenetic protein 4, respectively. After being inhaled in a bleomycin model, reverses mitochondrial dysfunction through ameliorating nicotinamide adenine dinucleotide biosynthesis, which inhibits accelerated senescence cells. Concurrently, pathological remodeling fibroblast activation induced by are terminated, ultimately prompting regeneration. Our data demonstrated that mRNA-LNP system exhibited high expression lung cells, markedly extricated collapse prolonged survival mice, providing clinically viable strategy against IPF.
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