Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury

doi:10.1016/j.jmst.2022.08.043

J. Mater. Sci. Technol. ›› 2023, Vol. 141: 21-31.DOI: 10.1016/j.jmst.2022.08.043

• Research Article • Previous Articles Next Articles

Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury

Xinxin Liu^a,b,1, Xuwei Ling^c,1, Jiachen He^c,1, Xingzhi Liu^d,e, Lin Wang^c, Huiling Liu^c, Chang Liu^c, Yi Wang^c, Xiao Lin^c,*, Chunhua Ling^a,*, Qin Shi^c,f,*

^aDepartment of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215031, China;
^bDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Gannan Medical University/Gannan Branch of National Clinical Research Center for Geriatrics, Ganzhou 341000, China;
^cDepartment of Orthopedics, the First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, Suzhou 215031, China;
^dSchool of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Suzhou 215123, China;
^eUniversity of Science and Technology of China, Hefei 230026, China;
^fNational Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215031, China

Received:2022-04-28 Revised:2022-08-07 Accepted:2022-08-29 Published:2023-04-01 Online:2022-10-28
Contact: *E-mail addresses: xlin@suda.edu.cn (X. Lin), lingchunhua@suda.edu.cn (C. Ling), shiqin@suda.edu.cn (Q. Shi)
About author:1 These authors contributed equally to this work.

Abstract

Abstract: 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.

Key words: Acute lung injury, Piezo1, Nanoparticle carrier, NF-κB, ERK1/2, GsMTx4

Xinxin Liu, Xuwei Ling, Jiachen He, Xingzhi Liu, Lin Wang, Huiling Liu, Chang Liu, Yi Wang, Xiao Lin, Chunhua Ling, Qin Shi. Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury[J]. J. Mater. Sci. Technol., 2023, 141: 21-31.

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Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury

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