Jie-Mei Li,1,2,* Lu Zhang,1,2,* Sheng-Lin Pei,1,3 Liang Guo,1,3 Hong-Lei Shen,1,2 Jing He,1,2 You-Yuan Guo,1,2 Wei-Qing Zhang,4 Fei Lin1,2 

1Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 2Guangxi Health Commission Key Laboratory of Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, Guangxi, People’s Republic of China; 3Guangxi Clinical Research Center for Anesthesiology, Nanning, Guangxi, People’s Republic of China; 4Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Fei Lin, Department of Anesthesiology, Guangxi Medical University Cancer Hospital, No. 71 hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +8613707886172, Fax +0086-771-536412, Email linfei@gxmu.edu.cn Wei-Qing Zhang, Department of Experimental Research, Guangxi Medical University Cancer Hospital, No. 71 hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email zhangweiqing2008@hotmail.com

Introduction: Lung injury, a common complication of sepsis, arises from elevated reactive oxygen species (ROS), mitochondrial dysfunction, and cell death driven by inflammation. In this study, a novel class of ultrasmall nanoparticles (Cu4.5O USNPs) was developed to address sepsis-induced lung injury (SILI).
Methods: The synthesized nanoparticles were thoroughly characterized to assess their properties. In vitro experiments were conducted to determine the biologically effective concentration and elucidate the anti-inflammatory mechanism of action. These findings were further supported by in vivo studies, showcasing the material’s efficacy in mitigating SILI.
Results: The Cu4.5O USNPs demonstrated remarkable scavenging capabilities for hydrogen peroxide (H2O2), superoxide anions (O2−), and hydroxyl radicals (·OH), attributed to their catalase (CAT)- and superoxide dismutase (SOD)-like activities. Additionally, the nanoparticles exhibited strong anti-inflammatory effects, preserved mitochondrial homeostasis through potent ROS scavenging, and significantly reduced cell death. In vivo studies on mice further validated their protective role against SILI.
The conclusion: This study highlights the therapeutic potential of Cu4.5O USNPs in treating sepsis-induced lung injury by effectively scavenging ROS and reducing cell death. These findings provide compelling evidence for the future use of copper-based nanoparticles as antioxidant therapeutics.

Keywords: ultrasmall copper-based nanoparticles, mitochondria, reactive oxygen species scavenging, lung injury, anti-inflammation