Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury

Inhaled drug-containing nanocarriers have been well applied as an important strategy in pulmonary diseases. Acute lung injury (ALI) is characterized by abnormal lung tension and complex pathogenesis, with high mortality because of the limitations of targeted intervention. Accordingly, in the present study, we first identified that the mechanosensitive ion channel Piezo1 participated in the ALI-associated processes induced by lipopolysaccharide (LPS) in vitro and in vivo. Then, chitosan-stabilized bovine serum albumin nanoparticles (NCs) emulsified with the Piezo1 inhibitor GsMTx4 (NC-GsMTx4) were generated and exhibited excellent biocompatibility and biological function. Through aerosol inhalation, NC-GsMTx4 improved lung injury and inhibited cell apoptosis in LPS-stressed ALI mice and alleviated pulmonary fibrosis during the later stage of ALI. Mechanistically, GsMTx4 could regulate inflammation and apoptosis in lung epithelial cells via NF-κB and ERK1/2 signaling. In summary, our findings provide new insights into the pathological mechanisms of Piezo1 in ALI progression, and nebulized inhalation of NC-GsMTx4 offers a prospective platform for targeting Piezo1 to treat ALI efficiently and conveniently.