title: Non-invasively differentiating extent of liver fibrosis by visualizing hepatic integrin αvβ3 expression with an MRI modality in mice.
abstract: To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis.
  
  
  
  Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment.
  
  
  
  Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis.
  
  
  
  The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.
authors.affiliation: Department of Gastroenterology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China; Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China; Shanghai Institute of Liver Diseases, Shanghai, China. Electronic address: wang.jiyao@zs-hospital.sh.cn.
authors.forename: Jiyao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Shanghai Institute of Liver Diseases, Shanghai, China; Key Laboratory of Medical Molecular Virology, Ministries of Education and Public Health, Department of Medical Microbiology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China.
authors.forename: Shengdi
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Radiology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Rao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Xihui
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Jin
mesh_terms: D000818:Animals; D050091:Dendrimers / Q000737:chemistry*; D055166:Hepatic Stellate Cells / Q000473:pathology; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D010456:Peptides, Cyclic / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C550210:cyclo(Arg-Gly-Asp-Tyr-Lys)
keywords: Hepatic stellate cells; Integrin αvβ3; Liver fibrosis; MRI modality; Nanoprobe