OBJECTIVE To develop novel copper glycyrrhizate （GC） nanoparticles via hybridization of glycyrrhizic acid （GA） with copper, and to evaluate their therapeutic efficacy against drug-resistant bacterial infections.

METHODS Copper chloride dihydrate （CuCl₂·2H₂O） and GA were taken as raw materials to prepare GC nanoparticles.The material properties of the nanoparticles were characterized by the Zeta potential analyzer. With saline as the control group, the antibacterial properties of GC nanoparticles against methicillin-resistant Staphylococcus aureus （MRSA） were evaluated through the scanning electron microscopy （SEM） and the plate count method. The antibacterial mechanism of GC nanoparticles was investigated via high-throughput transcriptomic sequencing. A mouse skin MRSA wound model was developed to evaluate the in vivo antibacterial efficacy of GC. At the end of the observation period, skin wound tissues were collected for colony plate counting and histological staining evaluation.

RESULTS  Copper ions complexed with GA to form GC nanoparticles. The Zeta potential of the nanoparticles was （−20.64±1.37） mV. The results of in vitro colony plate counting and SEM demonstrated the excellent antibacterial properties of the nanoparticles under acidic pH conditions. High-throughput transcriptomic sequencing results further revealed that the antibacterial mechanism involved a cuproptosis-like death in bacteria.In the mouse model of MRSA-infected skin wounds, H&E staining and Masson staining revealed better wound healing in the GC treatment group. Additionally, H&E staining of major organs also confirmed the good biosafety of these nanoparticles.

CONCLUSION  GC nanoparticles exhibit good antibacterial properties against drug-resistant bacteria and can effectively promote the healing of infected wounds, thereby holding potential for clinical application.