Han Feifei, Wang Haiping, Wang Li, Fan Limei, Peng Sibei, Hou Xiaoying, Shu Xiji, Sun Binlian, Liu Yuchen
Cancer Institute, School of Medicine, Jianghan University, Wuhan, Hubei, 430056, People's Republic of China.
Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan, Hubei, 430056, People's Republic of China.
Int J Nanomedicine. 2025 May 30;20:6949-6962. doi: 10.2147/IJN.S515107. eCollection 2025.
Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by excessive fat accumulation in the liver, is the most prevalent cause of chronic liver disease globally. The clinical use of pharmacological agents such as silibinin and sorafenib is limited due to poor water solubility, low bioavailability, and potential side effects, necessitating innovative therapeutic approaches.
In this study, we developed self-assembled, carrier-free microparticles of silibinin and sorafenib (SIL-SOR-MPs) using magnetic stirring and evaluated their therapeutic effects on MASLD both in vitro and in vivo.
Compared to free SIL and free SOR, SIL-SOR-MPs significantly reduced lipid accumulation in HepG2 cells and effectively alleviated hepatic steatosis and liver damage in mice. Mechanistic investigations further showed that SIL-SOR-MPs more effectively down-regulated lipid synthesis genes and up-regulated genes involved in lipid oxidation.
In summary, our study highlights that carrier-free SIL-SOR-MPs demonstrate the ability to reverse the progression of MASLD and present a promising therapeutic strategy.
代谢功能障碍相关脂肪性肝病（MASLD）以肝脏中脂肪过度积累为特征，是全球慢性肝病最常见的病因。水飞蓟宾和索拉非尼等药物由于水溶性差、生物利用度低和潜在副作用，其临床应用受到限制，因此需要创新的治疗方法。
在本研究中，我们通过磁力搅拌制备了水飞蓟宾和索拉非尼的自组装无载体微粒（SIL-SOR-MPs），并在体外和体内评估了它们对MASLD的治疗效果。
与游离水飞蓟宾（SIL）和游离索拉非尼（SOR）相比，SIL-SOR-MPs显著降低了HepG2细胞中的脂质积累，并有效减轻了小鼠的肝脂肪变性和肝损伤。机制研究进一步表明，SIL-SOR-MPs能更有效地下调脂质合成基因，并上调参与脂质氧化的基因。
总之，我们的研究表明，无载体的SIL-SOR-MPs具有逆转MASLD进展的能力，是一种很有前景的治疗策略。
