Lung-Targeting Interleukin-10 mRNA Lipid Nanoparticles Ameliorate Acute Lung Injury

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pulmonary Medicine

Background:

• Acute Respiratory Distress Syndrome (ARDS) is a severe form of Acute Lung Injury (ALI) with high mortality.
• Current treatments for ALI/ARDS lack specific pharmacological therapies.
• There is a critical need for effective therapeutic strategies to manage ALI/ARDS.

Purpose of the Study:

• To develop and evaluate a lung-targeted mRNA-sulfonium lipid nanoparticle (mRNA/sLNP) delivery system for ALI treatment.
• To investigate the therapeutic potential of interleukin-10 (IL-10) mRNA delivered via sLNPs in an ALI mouse model.

Main Methods:

• Optimization of sulfonium lipid structures for sLNP formulation.
• Comprehensive characterization of the optimized sLNP.
• Loading of IL-10 mRNA into sLNPs (IL-10/sLNP).
• Evaluation of IL-10/sLNP in a lipopolysaccharide (LPS)-induced ALI mouse model.

Main Results:

• The developed IL-10/sLNP system demonstrated both prophylactic and therapeutic efficacy in the ALI mouse model.
• Significant attenuation of pulmonary and systemic inflammation was observed.
• Restoration of lung barrier integrity and reduction in tissue injury were achieved.

Conclusions:

• Lung-targeted mRNA/sLNP delivery is a viable strategy for treating ALI.
• IL-10/sLNP therapy effectively mitigates inflammation and lung injury in a preclinical ALI model.
• This approach holds potential for developing novel pharmacological treatments for ARDS.