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Published on: February 26, 2017
Lung-Targeting Interleukin-10 mRNA Lipid Nanoparticles Ameliorate Acute Lung Injury
Yuqin Men1, David O Popoola1, Yuqi Song2
1Department of Pharmacology, The State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Abstract:
Acute respiratory distress syndrome (ARDS) is the most severe manifestation of acute lung injury (ALI), characterized by diffuse pulmonary inflammation, impaired gas exchange, and high morbidity and mortality. Despite its clinical significance, no specific or effective pharmacological therapies are currently available for its treatment. In this study, we developed a lung-targeted mRNA-sulfonium lipid nanoparticle (mRNA/sLNP) delivery system for the treatment of ALI in a mouse model. We first optimized sulfonium lipid structures, and the optimized sLNP was comprehensively characterized and subsequently loaded with interleukin-10 (IL-10) mRNA. In a lipopolysaccharide (LPS)-induced ALI mouse model, IL-10/sLNP demonstrated both prophylactic and therapeutic efficacy, significantly attenuating pulmonary and systemic inflammation, restoring barrier integrity, and reducing tissue injury.
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