Non-invasively differentiating extent of liver fibrosis by visualizing hepatic integrin αvβ3 expression with an MRI modality in mice
Non-invasively differentiating extent of liver fibrosis by visualizing hepatic integrin αvβ3 expression with an MRI modality in mice
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DOI：
10.1016/j.biomaterials.2016.06.026
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发表时间：
2016-09-01
期刊：
影响因子：
14
通讯作者：
Jin, Qu
中科院分区：
文献类型：
--
作者：
Li, Feng;Yan, Huihui;Jin, Qu
目的：探索用环状精氨酸-甘氨酸-天冬氨酸五肽（cRGDyK）标记的树枝状聚合物纳米探针作为磁共振成像（MRI）示踪剂非侵入性区分肝纤维化程度的潜力。方法：用cRGDyK（Den-RGD）标记合成树枝状聚合物纳米探针以形成肝星状细胞（HSC）特异性MRI示踪剂制剂。MRI模式是采用可视化肝Den-RGD沉积在小鼠模型中的肝纤维化引起的硫代乙酰胺treatment.Results：Den-RGD结合活化的HSC通过整合素043受体。用cRGDyK标记纳米探针增加了它们与活化的HSC的亲和力并加速了它们被活化的HSC摄取。静脉注射Den-RGD纳米探针后，大部分沉积在肝纤维化区域，且沉积量与肝纤维化程度相关。在纤维化肝脏中，发现大多数摄取Den-RGD的细胞是活化的HSC。Den-RGD作为示踪剂的MRI模式表明，相对肝脏T1加权MR信号值增加与肝纤维化的严重程度平行。结论：Den-RGD沉积的程度反映了整合素α v β 3在活化的HSC中的表达，Den-RGD似乎是一种有用的MRI示踪剂制剂，可以无创地定量评估肝纤维化的程度。(C)2016爱思唯尔有限公司版权所有
Aims: 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.Methods: 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.Results: Den-RGD bound to activated HSCs via integrin 043 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 Tl-weighed MR signal value was increased in parallel with the severity of liver fibrosis.Conclusion: The extent of Den-RGD deposition reflects integrin alpha v beta 3 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. (C) 2016 Elsevier Ltd. All rights reserved.