Han-mei Li,1,* Ju-ying Zhang,1,* Xiao-qing Wang,1 Li-tao Ye,1 Bo Ren,1 Yi-han Leng,1 Ji-xuan Zhang,2 You Yang,1 Qiong Jiang,1 Lin-li Feng,1 Yang Li,2 Jin-hong Yu1 

1Department of Ultrasound, Affiliated Hospital of North Sichuan Medical College, Innovation Centre for Science and Technology of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jin-hong Yu, Email yujinhong@nsmc.edu.cn Yang Li, Email 552410618@qq.com

Objective: Liver fibrosis replaces healthy tissue with scar tissue, potentially leading to cirrhosis and cancer. ROS drive this process by activating hepatic stellate cells. This study tests the hepatoprotective effects of PDA@CeO2 nanoparticles in scavenging ROS, inhibiting HSC activation, and delaying fibrosis, using 2D-SWE to assess treatment efficacy.
Methods: In vitro, flow cytometry evaluated ROS levels in HSCs, scratch assays assessed migration, and α-SMA expression confirmed activation. In vivo, PDA@CeO2 NPs were tested in rats with CCl4-induced liver fibrosis, with effects monitored by 2D-SWE. Histopathological staining and fibrosis markers (Collagen I, α-SMA, TGF-β/Smad3, NOX4) assessed fibrosis progression.
Results: In vitro, PDA@CeO2 reduced ROS levels and inhibited HSC migration, with decreased α-SMA expression indicating suppressed activation. In vivo, PDA@CeO2 treatment in CCl4-induced liver fibrosis rats reduced fibrosis markers. 2D-SWE showed improved liver stiffness, and histopathological analysis revealed reduced fibrosis and inflammation. The therapeutic effects were linked to modulation of the NOX4-TGF-β/Smad3 pathway, attenuating fibrosis progression.
Conclusion: This study demonstrates the potential of PDA@CeO2 NPs as a novel treatment for liver fibrosis. These nanoparticles scavenge ROS and modulate inflammatory pathways, targeting key signaling mechanisms like the NOX4-TGF-β/Smad3 pathway. PDA@CeO2 NPs offer a promising strategy for attenuating fibrosis at cellular and molecular levels. Additionally, 2D-SWE provides a non-invasive tool for monitoring therapeutic outcomes, positioning PDA@CeO2 NPs as a promising candidate for future clinical liver fibrosis treatments.

Keywords: PDA@CeO2, hepatic fibrosis, 2D-SWE, hepatic stellate cells