Feng Xiaoying, Dai Ling, Guo Yanfang, Zhong Liuting, Zheng Yuxiu, Feng Senling, Cao Liping, Yuan Zhongwen
Department of Pharmacy, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China.
School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
Mater Today Bio. 2025 Jun 27;33:102031. doi: 10.1016/j.mtbio.2025.102031. eCollection 2025 Aug.
Intrahepatic cholestasis in pregnancy (ICP) is a characteristic disease during the perinatal period; however, its therapy remains unsatisfactory, and the pathogenesis remains unclear. The ameliorative effect of naturally occurring quercetin 7-rhamnoside (Q7R) in cholestasis has been established. In this study, we aimed to establish a nanoparticle-based peptide, A20FMDV2-modified liposome (t-QL), to encapsulate and deliver Q7R. Q7R bioavailability improved significantly when liposomes were used as carriers. This peptide A20FMDV2-modified nanosystem targeted integrin αvβ6 on biliary epithelial cells and improved stillbirth rates and liver function indicators better than free Q7R without a carrier. Q7R improved ICP by regulating mitochondrial function and bile metabolism. Our nanosystem provides a promising nanotherapeutic strategy for applying Q7R in ICP. We also elucidated a therapeutic mechanism underlying the action of ICP by simultaneously targeting mitochondrial structure and function, as well as bile acid metabolism.
妊娠期肝内胆汁淤积症(ICP)是围产期的一种特征性疾病;然而,其治疗效果仍不尽人意,发病机制也尚不清楚。天然存在的槲皮素7-鼠李糖苷(Q7R)对胆汁淤积的改善作用已得到证实。在本研究中,我们旨在制备一种基于纳米颗粒的肽A20FMDV2修饰脂质体(t-QL),用于包封和递送Q7R。当脂质体用作载体时,Q7R的生物利用度显著提高。这种肽A20FMDV2修饰的纳米系统靶向胆管上皮细胞上的整合素αvβ6,比无载体的游离Q7R能更好地改善死产率和肝功能指标。Q7R通过调节线粒体功能和胆汁代谢改善ICP。我们的纳米系统为Q7R在ICP中的应用提供了一种有前景的纳米治疗策略。我们还通过同时靶向线粒体结构和功能以及胆汁酸代谢,阐明了ICP作用的治疗机制。