Abstract
Hepatic fibrosis (HF), as the only reversible process of chronic liver disease, remains a big diagnostic challenge. Development of noninvasive and effective methods to assess quantitatively early-stage HF is of great clinical importance. Compared with conventional diagnostic methods, near-infrared fluorescence imaging (NIR) and magnetic resonance imaging (MRI) could offer highly sensitive and spatial resolution signals for HF detection. However, precise detection using contrast agents is not possible. Superparamagnetic iron oxide (SPIO) nanoparticles have low toxicity, high sensitivity and excellent biocompatibility. Integration of Fe3O4 nanoparticles and indocyanine green (ICG), coupled with targeting ligand of integrin αvβ3, arginine–glycine–aspartic acid (RGD) expressed on hepatic stellate cells (HSCs), were used to detect HF. Both in vivo and in vitro results showed that the SPIO@SiO2–ICG–RGD had high stability and low cytotoxicity. The biodistribution of SPIO@SiO2–ICG–RGD was significantly different between mice with HF and healthy controls. SPIO@SiO2–ICG–RGD was characterized and the results of imaging in vitro and in vivo demonstrated the expression of integrin αvβ3 on activated HSCs. These data suggest that our SPIO@SiO2–ICG–RGD probe could be used for the diagnosis of early-stage HF. This new nanoprobe with a dual-modality imaging approach holds great potential for the diagnosis and classification of HF.
Highlights
Hepatic brosis (HF) is a key stage in the progression of chronic liver disease,[1,2] which can aggravate to cirrhosis and liver cancer
In the UVvis spectrum, absorption peaks were detected at 712 nm and 779 nm, which corresponded to Superparamagnetic iron oxide (SPIO) and indocyanine green (ICG), respectively (Fig. 2E)
X-ray photoelectron spectroscopy (XPS) indicated that iron, carbon, oxygen, nitrogen, and silicon were present in the core–shell composite SPIO@SiO2 (Fig. 2F)
Summary
Hepatic brosis (HF) is a key stage in the progression of chronic liver disease,[1,2] which can aggravate to cirrhosis and liver cancer. Liver injury initiates a cascade of brogenic processes initiated by in ammatory and brogenic signals.[3,4] In response to a persistent liver injury, macrophages[5,6] initiate the recruitment and transformation of resident quiescent hepatic stellate cells (HSCs)[7,8] to a myo broblast phenotype, which is highly activated, proliferative, motile, and contractile.[9] The cells of this phenotype are a major source of a redundant extracellular matrix (ECM).[10,11] Accumulation of the ECM is the main reason for HF induction.[3] In this process, integrin avb[3] is expressed by HSCs. Integrin avb[3] enhances the adhesion and migration of HSCs, which bind to the ECM,[12,13,14] whereas integrin avb[3] is not expressed by hepatocytes. Integrin avb[3] can be used as a unique target to activate HSCs, which induce brogenesis in the liver. The targeting ligand of integrin avb[3] is a sequence of three amino acids: arginine– glycine–aspartic acid (RGD).[15,16,17]
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