1(Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China) 2(Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China)
Abstract：This work is aimed to investigate the effect of dimercaptosuccinic acid-magnetite nanoparticles (DMSA-Fe3O4) on hepatic sinusoid endothelial cells (HHSECs) in vitro and in vivo. Transmission electron microscopy and nanoparticle tracking analysis were applied to characterize the particle size and surface property. Real-time cellular analysis assay, flow cytometry, quantitative real-time PCR (q-PCR) and Prussian blue staining were applied to analyze the effect of DMSA-Fe3O4 to HHSECs with the concentration from 0 to 200 μg/mL. DMSA-Fe3O4 with the dose of 1 mg/kg was injected into mice through the tail vein to analyze liver damage. For cell experiments, n=3; For animal experiments, n=4. HHSECs engulfed DMSA-Fe3O4 in a dose and time dependent manner, with cell viability decreasing to 37.3% of that for control group. DMSA-Fe3O4 engulfment increased the intracellular ROS of HHSECs to 1.41 folds. The expression of HO-1 of the cellswas significantly increased to 20.8 folds of the control group, the expression of HIF-1α was increased to 2.01 folds of the control group,the expression of VEGF was increased to 4.2 folds of the control group. DMSA-Fe3O4 were observed to accumulate in endothelial and Kupffer cells and induced liver damage on the 2nd day after the fourth injection. The amount of DMSA-Fe3O4 in the liver decreased significantly on day 158 and the hepatic damage was recovered. The DMSA-Fe3O4 nanoparticles was up-taken by HHSECs and induced cell oxidation related injury.In conclusion, multiple intravenous administrations of DMSA-Fe3O4 induced nanoparticle accumulation in the liver and its injury, which was recovered as DMSA-Fe3O4 being expelled from the liver over time.
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