Mannose-modified exosomes loaded with MiR-23b-3p target alveolar macrophages to alleviate acute lung injury in Sepsis.

Summary

miR-23b is downregulated in macrophages during sepsis-related ALI; intratracheal miR-23b mimics alleviate injury by suppressing M1 activation via the Lpar1–NF-κB pathway. Mannose-modified MSC-derived exosomes enable targeted delivery to macrophages, offering a low-immunogenic platform for pulmonary miRNA therapy.

Key Findings

• miR-23b expression is reduced in macrophages within ALI tissue.
• Intratracheal miR-23b mimics alleviate ALI by suppressing M1 macrophage activation via the Lpar1–NF-κB pathway.
• Mannose-modified MSC-derived exosomes enable targeted delivery of miR-23b to macrophages, reducing immunogenicity concerns.
• The targeted exosomal miRNA strategy mitigated sepsis-induced lung injury in vivo.

Clinical Implications

While preclinical, the platform suggests a route to reduce inflammatory lung damage in sepsis by precisely delivering anti-inflammatory miRNA to alveolar macrophages, potentially lowering doses and systemic toxicity.

Limitations

• Preclinical animal study without human safety, dosing, or pharmacokinetic data.
• Comparative efficacy versus standard anti-inflammatory or anti-cytokine therapies not assessed.

Future Directions

Define safety, biodistribution, and dosing in larger animals; optimize exosome manufacturing; and conduct early-phase clinical trials in sepsis-related ALI.