Self-Propelled Proteomotors with Active Cell-Free mtDNA Clearance for Enhanced Therapy of Sepsis-Associated Acute Lung Injury

Acute lung injury (ALI) is a frequent and serious complication of sepsis with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis-associated ALI can help develop new therapeutic strategies. Herein, the crucial role of cell-free mitochondrial DNA (cf-m...

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Bibliographic Details
Published in:Advanced science 2023-09, Vol.10 (27), p.e2301635-e2301635
Main Authors: Huang, Weichang, Wen, Lihong, Tian, Hao, Jiang, Jiamiao, Liu, Meihuan, Ye, Yicheng, Gao, Junbin, Zhang, Ruotian, Wang, Fei, Li, Huaan, Shen, Lihan, Peng, Fei, Tu, Yingfeng
Format: Article
Language:English
Subjects:
cell‐free mitochondrial DNA
Cystic fibrosis
Cytokines
Disease
DNase‐I
Efficiency
Enzymes
Inflammation
Lungs
Mitochondrial DNA
Mortality
nanomotors
Nanoparticles
pulmonary delivery
self‐propulsion
Sepsis
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Summary:Acute lung injury (ALI) is a frequent and serious complication of sepsis with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis-associated ALI can help develop new therapeutic strategies. Herein, the crucial role of cell-free mitochondrial DNA (cf-mtDNA) in the regulation of alveolar macrophage activation during sepsis-associated ALI is identified. Most importantly, a biocompatible hybrid protein nanomotor (NM) composed of recombinant deoxyribonuclease I (DNase-I) and human serum albumin (HSA) via glutaraldehyde-mediated crosslinking is prepared to obtain an inhalable nanotherapeutic platform targeting pulmonary cf-mtDNA clearance. The synthesized DNase-I/HSA NMs are endowed with self-propulsive capability and demonstrate superior performances in stability, DNA hydrolysis, and biosafety. Pulmonary delivery of DNase-I/HSA NMs effectively eliminates cf-mtDNAs in the lungs, and also improves sepsis survival by attenuating pulmonary inflammation and lung injury. Therefore, pulmonary cf-mtDNA clearance strategy using DNase-I/HSA NMs is considered to be an attractive approach for sepsis-associated ALI.
ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202301635