Li Han-Mei, Zhang Ju-Ying, Wang Xiao-Qing, Ye Li-Tao, Ren Bo, Leng Yi-Han, Zhang Ji-Xuan, Yang You, Jiang Qiong, Feng Lin-Li, Li Yang, Yu Jin-Hong
Department 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.
Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China.
Int J Nanomedicine. 2025 Jul 15;20:9073-9091. doi: 10.2147/IJN.S521372. eCollection 2025.
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@CeO nanoparticles in scavenging ROS, inhibiting HSC activation, and delaying fibrosis, using 2D-SWE to assess treatment efficacy.
In vitro, flow cytometry evaluated ROS levels in HSCs, scratch assays assessed migration, and α-SMA expression confirmed activation. In vivo, PDA@CeO 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.
In vitro, PDA@CeO reduced ROS levels and inhibited HSC migration, with decreased α-SMA expression indicating suppressed activation. In vivo, PDA@CeO 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.
This study demonstrates the potential of PDA@CeO 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@CeO 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@CeO NPs as a promising candidate for future clinical liver fibrosis treatments.
肝纤维化用瘢痕组织替代健康组织，可能导致肝硬化和癌症。活性氧通过激活肝星状细胞驱动这一过程。本研究使用二维剪切波弹性成像（2D-SWE）评估治疗效果，测试PDA@CeO纳米颗粒在清除活性氧、抑制肝星状细胞激活和延缓纤维化方面的肝保护作用。
在体外，流式细胞术评估肝星状细胞中的活性氧水平，划痕试验评估迁移，α-平滑肌肌动蛋白（α-SMA）表达确认激活情况。在体内，对四氯化碳诱导的肝纤维化大鼠测试PDA@CeO纳米颗粒，通过二维剪切波弹性成像监测效果。组织病理学染色和纤维化标志物（I型胶原、α-SMA、转化生长因子-β/Smad3、NADPH氧化酶4（NOX4））评估纤维化进展。
在体外，PDA@CeO降低了活性氧水平，抑制了肝星状细胞迁移，α-SMA表达降低表明激活受到抑制。在体内，对四氯化碳诱导的肝纤维化大鼠进行PDA@CeO治疗降低了纤维化标志物水平。二维剪切波弹性成像显示肝脏硬度改善，组织病理学分析显示纤维化和炎症减轻。治疗效果与NOX4-转化生长因子-β/Smad3通路的调节有关，减轻了纤维化进展。
本研究证明了PDA@CeO纳米颗粒作为肝纤维化新疗法的潜力。这些纳米颗粒清除活性氧并调节炎症通路，靶向NOX4-转化生长因子-β/Smad3通路等关键信号机制。PDA@CeO纳米颗粒为在细胞和分子水平减轻纤维化提供了一种有前景的策略。此外，二维剪切波弹性成像为监测治疗结果提供了一种非侵入性工具，使PDA@CeO纳米颗粒成为未来临床肝纤维化治疗的有希望的候选者。
