1. Academic Validation
  2. Archaea-inspired deoxyribonuclease I liposomes prevent multiple organ dysfunction in sepsis

Archaea-inspired deoxyribonuclease I liposomes prevent multiple organ dysfunction in sepsis

  • J Control Release. 2025 Apr 10:380:1109-1126. doi: 10.1016/j.jconrel.2025.02.050.
Xinze Li 1 Fan Wu 1 Dedong Yu 2 Xiayi Su 1 Kaikai Wang 1 Zhiwei Huang 3 Zhongqiu Lu 4
Affiliations

Affiliations

  • 1 Department of Emergency, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325035, China.
  • 2 Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
  • 3 Central Laboratory, the Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui 323000, China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: hzwpharm@163.com.
  • 4 Department of Emergency, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325035, China. Electronic address: lzhq@wmu.edu.cn.
Abstract

Neutrophil extracellular traps (NETs) and circulating cell-free DNA (cfDNA) are pivotal in driving excessive inflammation and organ damage during sepsis, with their levels correlating positively with sepsis severity in both patients and murine models. Despite the ability of deoxyribonuclease I (DNase I) to degrade NETs and cfDNA, its short half-life and rapid degradation limit its therapeutic effectiveness. To address this challenge, we developed a methyl-branched Liposome fused with a red blood cell membrane for the systemic delivery of DNase I (DNase I/Rm-Lipo). The efficacy of DNase I/Rm-Lipo was evaluated in the stimulated immune cells and septic model. The data confirmed that DNase I/Rm-Lipo efficiently removed excess NETs and cfDNA in activated neutrophils. Following injection, DNase I/Rm-Lipo exhibited an extended circulation time, effectively suppressing neutrophil activation and regulating macrophage polarization to mitigate inflammation and prevent organ dysfunction in septic mice. These findings highlight the therapeutic potential of DNase I/Rm-Lipo as a promising candidate for sepsis management by targeting the degradation of NETs and cfDNA.

Keywords

Cell-free DNA; DNase I; Erythrocyte membrane; Methylated liposomes; Neutrophil extracellular traps.

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