Magnetic Endoglin Aptamer Probe Targeting Liver Cancer Research

Liver cancer is our country and even the world’s most common cancer,is one of the primary cancer-related cause of death.Advanced liver cancer patients with high mortality,surgical resection is difficult,radiotherapy and chemotherapy are not effective,the chance of prognosis is poor.Early diagnosis of liver cancer and early treatment has become the key to improve the prognosis and survival rate of patients,but there is still a lack of high clinical specificity non-invasive means of early diagnosis.In recent years,the development of molecular imaging for the early diagnosis of malignant tumors increased new ideas,molecular targeted magnetic resonance imaging（Magnetic Resonance Imaging,MRI）technology will become an idear tumor targeting and non-invasive detection means.How to find a better specific liver cancer target,how to construct MRI imaging probes targeting liver cancer has become the focus of the current MRI molecular imaging.This study was prepared to synthesize an Endoglin aptamer modified magnetic chitosan nanoparticles which target tumor endothelial cells be used for liver tumor bearing mouse models to explore its target liver cancer MRI imaging capabilities.Objective To prepare an effectively targeting tumor vascular endothelial cells（mouse tumor vascular endothelial cells,m TEC）surface molecules-CD105 specific aptamer Endoglin magnetic imaging probe system（mEND-Fe₃O₄@CMCS）,explore the ability of mEND-Fe₃O₄@CMCS probe to targeting liver cancer through MRI imaging in vivo.Methods Fe₃O₄ magnetic nanoparticles was prepared by hydrotherm-al method;glutaraldehyde as a crosslinking agent by the emulsion crosslinking method of preparing Fe₃O₄@CMCS magnetic chitosan nanoparticles.The Endoglin aptamers will crosslinking by Sulfo-SMCC to modifications in Fe₃O₄@CMCS surface to synthesize mEND-Fe₃O₄@CMCS.By transmission electron microscopy and dynamic light scattering instrument on the morphology,the particle size and surface potential of mEND-Fe₃O₄@CMCS were characterized and analyzed.By Fourier transform infrared spectroscopy and thermal gravimetric analyzer mEND-Fe₃O₄@CMCS were further characterization analysis.The CCK-8 cytotoxicity assay evaluate the bio-security of mEND-Fe₃O₄@CMCS.By fluore-scence microscopy,flow cytometry,Prussian blue iron stain test and phagocytosis of intracellular iron content detection to detect the targeting ability of mEND-Fe₃O₄@CMCS probe to combined with CD105⁺tumor vascular endothelial cells（CD105⁺cells）.Clinical use of GE 3.0T MRI imaging system to analyze the m End-Fe₃O₄@CMCS in vivo imaging capabilities,observe the situation in vivo targeting efficiency and relaxation.HE staining verify mEND-Fe₃O₄@CMCS damage to vital organs whether the toxicity in mice.Results Successfully prepared mEND-Fe₃O₄@CMCS probe,diameter of about 87±1.66 nm,uniform distribution is relatively stable in serum,small cell toxicity.The mEND-Fe₃O₄@CMCS can effectively targeted the expression of CD105⁺tumor vascular endothelial cells.Through its GE 3.0T MRI imager imaging analysis,the mEND-Fe₃O₄@CMCS probe had high T2 relaxation efficiency,which can effectively targeted liver cancer and as a T2 contrast agents to improve the image contrast in mice transplanted tumor site.Conclusion Successfully prepared a magnetic Endoglin aptamer mEND-Fe₃O₄@CMCS probe to effective targeting vascular endothelial cells in mouse hepatoma,provides a targeting probe system can achieve early diagnosis of liver cancer which has an broad application prospect.