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Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury

Journal of Materials Science & Technology 2023年第10期141卷 21-31页

作者： Xinxin Liu Xuwei Ling Jiachen He Xingzhi Liu Lin Wang Huiling Liu Chang Liu Yi Wang Xiao Lin Chunhua Ling Qin Shi Department of Respiratory Medicine the First Affiliated Hospital of Soochow UniversitySuzhou 215031China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Gannan Medical University/Gannan Branch of National Clinical Research Center for GeriatricsGanzhou 341000China Department of Orthopedics the First Affiliated Hospital of Soochow UniversityOrthopedic Institute of Soochow UniversitySuzhou 215031China School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaSuzhou 215123China University of Science and Technology of China Hefei 230026China National Clinical Research Center for Hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215031China

Inhaled drug-containing nanocarriers have been well applied as an important strategy in pulmonary dis-eases.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 albu-min nanoparticles(NCs)emulsified with the Piezo1 inhibitor GsMTx4(NC-GsMTx4)were generated and exhibited excellent biocompatibility and biological function.Through aerosol inhalation,NC-GsMTx4 im-proved 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.

关键词： Acute lung injury Piezo1 Nanoparticle carrier NF-κB ERK1/2 GsMTx4

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