Journal
BIOMATERIALS
Volume 102, Issue -, Pages 162-174Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.06.026
Keywords
Nanoprobe; Hepatic stellate cells; Integrin alpha v beta 3; Liver fibrosis; MRI modality
Funding
- National Natural Science Foundation of China [30770970, 81270007, 81301875, 81272436, 81572356]
- Nano Science and Technology Projects of Shanghai Science and Technology Commission [12nm0501400]
- Shanghai Talent Development Funds [201304]
- Shanghai Rising-Star Program [13QA1400700]
- Shanghai Outstanding Young Talent Training Plan in Health System Grant [13YO56]
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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.
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