Jizhao Wang,1 Rui Zhu,2,3 Kaibo Yang,2,3 Zitong Lei,4 Xing Zhang,2,3 Yuchen Sun,5 Xiaozhi Zhang5 1Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Hepatobiliary Surgery and Liver Transplantation, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Key Laboratory of Surgical Critical Care and Life Support (Xi’an Jiaotong University), Ministry of Education, Xi’an, Shaanxi, People’s Republic of China; 4Department of Critical Care Nephrology and Blood Purification, The First Affiliated Hospital of Xi’an Jiao-Tong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 5Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Xiaozhi Zhang, Department of Radiation Oncology, First Affiliated Hospital of Xi’an Jiaotong University, No. 277, Yanta West Road, Xi’an, Shaanxi, 710061, Email [email protected]: In this study, we constructed baicalein (a traditional Chinese medicine)-loaded chitosan nanoparticles (a drug-delivery system) with great biocompatibility for the remission of Staphylococcus aureus-induced lung infection.Methods: The nanoparticles were prepared via a one-step reaction. Baicalein-release rates were studied via ultraviolet absorption assays. Morphology was characterized using AFM and TEM. The antibacterial mechanism of the nanoparticles was studied through ONPG, crystal violet staining, and live/dead bacterial staining assays, anti-inflammatory performance investigated via ELISA and WB assays, and in vivo anti-lung-infection capacity studied via H&E staining and ELISA kits.Results: The average size of the nanoparticles was uniform (~200 nm), and the zeta potential was about 18.5 ± 0.3 mV. The encapsulation efficiency was about 40%. The release of baicalein was > 80% under different temperatures and pH. Dry nanoparticles were also stable. The minimum inhibitory concentration against S. aureus was about 15 μg/mL. The maximum tolerable dose in vivo was 300 μg/kg. The nanoparticles exhibited outstanding anti-inflammatory and anti-lung-infection performance.Conclusion: The in vitro and in vivo results demonstrate that our drug-delivery system could be an efficient platform for the remission of bacterium-induced lung infection.Keywords: baicalein, Staphylococcus aureus, lung infectio