Ionizable lipid nanoparticles enhance lung delivery of gold nanoclusters for improving acute lung injury alleviation†

Acute lung injury (ALI) is one of the most common and highly prevailing respiratory system diseases. However, there is still a lack of effective specialized medicines for the treatment of ALI. Biocompatible gold nanoclusters (AuNCs) have shown great potential in alleviating ALI, but their lung-targeted delivery needs to be enhanced. In recent years, lipid nanoparticles (LNPs) have become the most promising delivery system for clinical application and achieved great success in mRNA vaccines during the COVID-19 pandemic. Herein, we constructed a lung-delivery formulation of AuNCs by encapsulating glutathione-coated gold nanoclusters (GA) in lung-delivery ionizable lipid nanoparticles (iLNPs) and termed it as 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 suggest that organ-selective iLNPs may be an ideal targeted delivery system for AuNCs, providing a powerful tool for translational applications of bioactive AuNCs.