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
AUTHORS (21)
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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