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

Abstract

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.

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential

“…DNase (deoxyribonuclease) is an enzyme that occurs naturally in the body and is involved in the breakdown of DNA. 242,243 It is produced by a variety of organisms, including bacteria, fungi, and animals, and still draws plenty of attraction even though it has been investigated in NETs study for years. Regarding the suppression of NETs, DNase is quite different from other NETs inhibitors since the focus of DNase is managed to extrude NETs instead of participating in the formation of NETs.…”