Engineered SPIONs functionalized with endothelin a receptor antagonist ameliorate liver fibrosis by inhibiting hepatic stellate cell activation

作     者：Marit ten Hove Andreas Smyris Richell Booijink Lydia Wachsmuth Uwe Hansen Lejla Alic Cornelius Faber Carsten Hӧltke Ruchi Bansal 

作者机构：Personalized Diagnostics and TherapeuticsDepartment of Bioengineering TechnologiesTechnical Medical CentreFaculty of Science and TechnologyUniversity of TwenteEnschedethe Netherlands Clinic of RadiologyUniversity Hospital MuensterMuensterGermany Institute for Musculoskeletal MedicineUniversity Hospital MuensterMuensterGermany Department of Magnetic Detection and ImagingTechnical Medical CentreFaculty of Science and TechnologyUniversity of TwenteEnschedethe Netherlands 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2024年第39卷第9期

页      面：406-426页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：UT-WWU HSCs University of Twente Twente Graduate School at the University of Twente 

主　　题：Endothelin A receptor SPIONs Hepatic stellate cells Liver fibrosis 

摘      要：Endothelin-1/endothelin A receptor(ET-1/ETAR)pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells(HSCs)-a key cell type involved in the pathogenesis of liver *** HSCs by blocking the ET-1/ETAR pathway using a selective ETAR antagonist(ERA)represents a promising therapeutic approach for liver ***,small-molecule ERAs possess limited clinical potential due to poor bioavailability,short half-life,and rapid renal *** improve the clinical applicability,we conjugated ERA to superparamagnetic iron-oxide nanoparticles(SPIONs)and investigated the therapeutic efficacy of ERA and ERA-SPIONs in vitro and in vivo and analyzed liver uptake by in vivo and ex vivo magnetic resonance imaging(MRI),HSCs-specific localization,and ET-1/ETAR-pathway antagonism in *** murine and human liver fibrosis/cirrhosis,we observed overexpression of ET-1 and ETAR that correlated with HSC activation,and HSC-specific localization of *** and successfully synthesized ERA-SPIONs demonstrated significant attenuation in TGFβ-induced HSC activation,ECM production,migration,and *** an acute CCl4-induced liver fibrosis mouse model,ERA-SPIONs exhibited higher liver uptake,HSC-specific localization,and ET-1/ETAR pathway *** resulted in significantly reduced liver-to-body weight ratio,plasma ALT levels,andα-SMA and collagen-I expression,indicating attenuation of liver *** conclusion,our study demonstrates that the delivery of ERA using SPIONs enhances the therapeutic efficacy of ERA in *** approach holds promise as a theranostic strategy for the MRI-based diagnosis and treatment of liver fibrosis.