| Objective:Vulnerable plaque is difficult to early imaging.Among all the cells in the formation of vulnerable plaque,macrophages accounted for the largest proportion and scavenger receptor A1（SR-A1）plays a major role in foam cell formation.To investigate the early imaging method of vulnerable plaques in the present research,we prepared an SR-targeted nanoparticle and used a foam cell model to verify the targetability of the nanomaterial.Methods:Raw264.7 macrophages were treated by Ox-LDL in the experimental group to induce macrophages into foam cells.The foam cell model was successfully established in the experimental group,and the model was qualitatively and quantitatively analyzed.Biomineralization was used to bond bovine serum albumin（BSA）with Mn and Bi,then added maleic anhydride to targeted scavenger receptor A（SR-A1）.The size and zeta potential of the nanoprobe was assessed by dynamic light scatter（DLS）and transmission electron microscopy（TEM）.The toxicity of the nanoprobe was tested by the CCK8method.The targeting ability of nanoparticles was also evaluated,and compared with the consequence of co-incubation vascular endothelial cells and smooth muscle cells with the nanoparticle.Finally,we used magnetic resonance imaging（MRI）and computed tomography（CT）to imagine different concentrations of nanoprobe.After incubating with nanoprobe in the experimental group and the control group macrophages,another MRI and CT scan was performed to observe the results of cell imaging.Results:Raw264.7 macrophages are characterized by lipid droplets in the cytoplasm after treatment with Ox-LDL to foam cells in the experimental group.Immunofluorescence analysis showed that the red fluorescence was more obvious than that of the control group which indicated that the expression of SR-A1（encoded by MSR1 gene）is higher.The difference was statistically significant.QPCR quantitative analysis obtained similar results.The nanoparticle of MnO2-Bi2S3@BSA-Mal was successfully prepared.The material has a diameter of about 50.7nm on DLS,which shows no difference from the results of TEM.The zeta potential is about-47.9m V.The results of cytotoxic test CCK8 showed that the macrophage vitality was more than 90%at the normal nanoprobe concentration use,which could be further used.The nanomaterials can strengthen T1 signal intensity on MRI.The signal intensity of macrophages in the experimental group is stronger than that in the control group,which proves that the cells absorb more materials and have better targeting.CT scan obtained similar results.To investigate the ability of different cells in the vascular wall to ingest nanomaterials,the nanomaterials were co-incubated with macrophages,vascular endothelial cells,and smooth muscle cells.The nanomaterials were mainly concentrated in macrophages,but less around the other two kinds of cells.Conclusion:MnO2-Bi2S3@BSA-Mal was successfully prepared which possesses appropriate size and toxicity.The ability to target foam cells is excellent.Besides,the nanomaterial can also increase the image contrast of MRI and CT,and imaging results are well at the cell level. |
