Ionizable Lipid Nanoparticles Enhance Lung-Delivery of Gold Nanocluster for Improving Acute Lung Injury Alleviation

Abstract

Acute lung injury (ALI) is one of the most common respiratory system diseases with high prevalence. However, there is still lacking of effective specialized medicines for the treatment of ALI. Biocompatible gold nanoclusters (AuNCs) showed high potential in alleviating ALI, but their lung-targeted delivery need to be enhanced. In recent years, lipid nanoparticles (LNP) have become the most promising delivery system for clinical application, and have achieved great success in mRNA vaccines during the COVID-19 pandemic. Herein, we constructed a lung-targeted formulation of AuNCs by encapsulating glutathione-coated gold nanocluster (GA) in lung-targeted ionizable lipid nanoparticle (iLNP) and named GA@iLNP. Results indicated that, GA@iLNP can promote the cellular uptake of GA and enhance the anti-inflammation efficiency in stimulated macrophages in vitro. In addition, iLNP encapsulation significantly increased the lung accumulation of GA in lipopolysaccharide (LPS)-induced ALI mice after intravenous injection, and enhanced the alleviations of inflammation and tissue damage in the lungs. These results implied that organ-selective iLNPs could be an ideal targeted delivery system for AuNCs, and provide a powerful tool for translational applications of bioactive AuNCs.